In a mountain village, inhabited half by identical young women and half by identical old women, live two unique individuals, Mana, a girl who has just turned fifteen, and Baba (Nanny in the English dub), the old woman who pampers Mana while keeping her shackled in bed. The secret the women keep, even from Mana, is that all the identical women are mermaids and that aged mermaids need to eat young immortal women to regain their youth. After Baba feeds the flesh of one of the mermaids to Mana, Yuta learns about their ultimate plan for Mana and tells her about it. While trying to stop Yuta and Mana from escaping, the women revert to their mermaid form and are unable to take human form again. Baba, also an immortal human, stays behind as Yuta and Mana leave. Yuta tells Mana that life as an immortal isn't all bad, but he still hopes to become mortal again.

In a flashback, Yuta remembers Rin, the daughter of the pirate chief of Toba island, and the ruthless rival pirates of Sakagami island. Isago, the wife of the Sakagami chief, convinces the chief to use his men to hunt mermaids. She also hires Yuta and some other men in a nearby port for the hunt. On Toba, Rin's father is gravely ill, so Rin leads the raiding parties on passing ships, demanding a tenth of their cargo as a toll, but killing no one. Yuta, drowned in a violent storm while mermaid hunting for Isago, washes up on Toba. As Rin places flowers on Yuta's grave the next day, he revives. For a time, Yuta lives and works with the Toba islanders. One day Isago sees Yuta and Rin in port. Surprised to see Yuta alive, Isago realizes he is immortal and believes he kept the mermaid she hired him to find. She follows them back to Toba and stabs Rin's father, telling Rin that only mermaid flesh can stop him from dying. In retaliation, Rin kills Isago.

Yuta and Rin take a fishing boat and capture a mermaid to save Rin's father. The Sakagami islanders, who followed them to sea, kill the mermaid and Yuta, taking Rin to Sakagami. Rin sees Isago there and realizes Isago is immortal. Isago reveals that she has been pregnant for three years by her previous husband, whom the Sakagami islanders killed, and that she needs mermaid flesh so she can finally give birth. A revived Yuta arrives to save Rin. The chief and his men alternately fight Yuta and Rin and eat mermaid flesh. Those who don't die from the mermaid flesh, including the chief, become Deformed Ones. Isago runs away and jumps off a cliff into the ocean. Yuta and Rin think Isago did it in desperation, but Isago, now in mermaid form, swims away trailed by two smaller forms. On Toba, Rin's father recovers on his own, without mermaid flesh. Back in the present, Mana asks Yuta how far the ocean goes.

A truck strikes and kills Mana. Shiina, the old doctor who examines her, tells the police and Yuta that she survived and wandered away. Shiina takes her corpse to Sawa, an old woman, and Towa, a young woman with a heavily bandaged right arm. As he begins to replace Towa's arm with Mana's, Mana revives. Yuta realizes that Shiina lied and follows him to Sawa's and Towa's house, where local legend says a mermaid is buried. Towa has a Deformed dog kill Yuta. When he revives, Shiina, Sawa, and Towa confine Yuta to a cell in the basement. Towa kills Mana, to have Shiina transplant her head onto Mana's body. Sawa tells Yuta that she and Towa are identical twins. When they were young, Sawa had given Towa medicine made of mermaid blood to save her from a terminal illness, making her ageless, but Deforming her arm. Rather than admit his daughter was partially Deformed, their father had told everyone that Towa had died and had confined her to the cell in the basement until his death.

Towa tells Sawa that revealing the mermaid's location will save Mana. Mana revives as they approach the mermaid tomb. Yuta arrives at the tomb and tells Towa that eating mermaid flesh will only complete her transformation into a Deformed One. He also says being immortal was lonely before he found Mana. Towa says immortality or transformation makes no difference and forces a piece of mermaid flesh on Sawa, explaining that Sawa had desired immortality. Too afraid to try it herself, Sawa had experimented on Towa, her biological twin. Then, while Towa had lived in confinement, Sawa had lived a full life. Towa wants Sawa to be immortal, as an old woman or as a monster. Sawa dies of a heart attack, denying Towa her revenge. Towa tells the others to burn the tomb, the house, and everything in them, including Towa. As they watch the fire burn, Shiina says that he had tried to convince Towa to escape with him when he was young. Towa had refused, saying she had to stay to get her revenge. Mana asks Yuta if being alone before was hard.

Yuta and Mana fall off a cliff chasing a butterfly. Mana is unconscious, but Yuta dies. A heavily bandaged man, Big Eyes, as nearby villagers call him, carries Mana to his cave. An old hunter from the village finds Yuta, but Yuta revives during his burial rites. That night when Mana awakens, Big Eyes tells her that she is safe. The next morning Big Eyes tells Mana that long ago he lived in a fishing village. He ate mermaid flesh, blacked out, and, regaining his senses, discovered everyone in his village had been killed. He ran into the mountains and had lived alone ever since. When Yuta and the hunter find Mana and Big Eyes, Big Eyes flees with Mana deep into the cave. There Mana stumbles upon the skeletons of villagers that Big Eyes has eaten. Big Eyes explains that he still blacks out. When the hunter shoots Big Eyes, Big Eyes goes berserk and runs away. Yuta catches and kills Big Eyes. Mana ponders that there are all sorts of Deformed Ones, all sorts of mermaids, and all sorts of Yutas.

In a flashback to the first year of the Tokugawa shogunate, when Yuta was 120, Yuta remembers Natsume, an apparently 12-year-old immortal girl who works in a market with an old man, whom she calls Pa and who purports to sell mermaid flesh. An itinerant monk who has been searching for Natsume finds her and cuts off her left arm. Yuta carries Natsume and her severed arm back to Pa, who reattaches her arm. In truth, the monk had used a piece of mermaid liver to resurrect Natsume for Pa. When the monk had decided to end Natsume's existence, Pa had run away with her. Yuta doubts destroying Natsume is the right thing to do and offers to take her with him. The monk attacks Natsume and removes the mermaid liver. When Pa sees that the monk has removed Natsume's liver, he picks her up and jumps off a cliff with her. Yuta finds Natsume alive at the base of the cliff, but she turns to bones in his arms. Back in the present, Mana asks Yuta if he thinks she has developed nicely.

Yuta and Mana meet Nanao, a 10-year-old boy carrying a cinerary box. Nanao was kidnapped by an unknown man with the help of his grandmother, but he escaped. Yuta and Mana take Nanao home, where Nanao's grandmother shows Yuta and Mana a photograph of Nanao's mother, who is not the woman Nanao calls Mother. Alone, Nanao's mother opens the cinerary box, revealing the skin of a scarred woman's face. The next day Mana and Nanao see Nanao's mother enter the cellar, but later the woman from the photo emerges with a bandage on one side of her face. In the cellar, Mana discovers surgical instruments and the skin from the face of Nanao's mother. Meanwhile Yuta has been following the kidnapper. When the woman with the bandage meets the kidnapper, Yuta overhears her call him Nanao and him call her Mother. The bandage slips from her face, revealing a scar. The older Nanao explains to Yuta that, 25 years ago, his mother ate mermaid flesh. Then eight years ago, his mother, who hadn't aged in 25 years, kidnapped his son.

In the cellar, the scarred woman attacks Mana, but Mana and Nanao escape. Then the woman uses the surgical instruments to remove the skin from her face and to replace it with the unscarred face, becoming the woman Nanao thinks is his mother. Not knowing the two women are the same person, Nanao tells her where the injured Mana is hiding. As Nanao's mother is dragging Mana to the cellar, Yuta and the older Nanao arrive. Mana throws the box with the scarred face outside, where it opens to allow Yuta to see its contents. Nanao's mother admits that she replaced the face scarred from mermaid poison with one she got from the corpse of a woman who washed ashore. Nanao's mother locks herself and Nanao in the cellar so the others cannot stop her from feeding him mermaid flesh. As the scar appears on her new face, she doubts that the mermaid flesh is not poison. Mana knocks the flesh from Nanao's hands as he tries to eat it. Nanao's mother gives him back to the older Nanao and walks off into the fog.

In a flashback to 60 years before, a girl, Nae, tells her servant, Sokichi, and Yuta that local villagers used mermaid ash to create the Red Valley, a field of perennially blooming red flowers. Elsewhere Yuta heard that a villager killed a nun to steal the ash, but the nun came back to life and killed many of the villagers. When Yuta leaves, Nae disappears. The village holds a funeral for her, even though there's no body. Over the decades, Eijiro, Nae's former fiance, buys the village land. In the present, Mana finds one of Eijiro's men beating a girl named Nae. Nae kills the man, but two other men kill Mana. Eijiro, who keeps Nae confined on his estate, realizes Mana is immortal when she revives. Meanwhile, Sokichi, having met up with Yuta, tells Yuta that Nae is still alive unchanged and leads him to Eijiro's house, where Eijiro's men capture them. Nae kills some of Eijiro's men and escapes with Mana. Eijiro orders his men to recapture Nae unharmed and to decapitate Yuta.

In flashback, Nae arranges a signal with Yuta if he wants to meet her in the Red Valley on the day he is to depart. Eijiro leaves the signal to test Nae's loyalty to him. When Nae goes to the Red Valley, Eijiro kills her. Eijiro thinks he can revive Nae with mermaid ash. He cannot find it, however, because Nae hid the remaining ash to keep her father from finding out that she used it to make the Red Valley. Eijiro looks for the ash for decades and finally finds it, using it to revive Nae's still pristine corpse in the Red Valley. In the present, Yuta and Sokichi escape Eijiro's men. Nae leads Mana to the Red Valley, but Eijiro intercepts them. When Nae and Mana try to proceed to the Red Valley, Eijiro draws a knife and stabs Nae, critically wounding her. Nae arrives in the Red Valley and remembers that Eijiro killed her there. When Yuta arrives and goes to Nae, she dies from her wound. As they leave, Yuta asks Mana if it's jealousy that makes her impatient with him. Mana asks Yuta if jealousy is some kind of dessert.

Yuta and Mana meet a boy, Masato, who is traveling to live with his mother. One night two years later, Masato stabs his mother in the chest, then cleans up the murder scene. The next morning, Masato's mother is alive again. The woman who runs the kitchen at a nearby construction site, where Yuta and Mana work, tells them that Masato's mother died in a boat accident, then came back to life. Later, Masato's mother notices that her chest wound isn't healing. Masato gives Yukie, the housekeeper, a piece of mermaid flesh, making her Deformed. Yuta arrives in time to kill Yukie, while Mana escapes to safety with Masato. Masato realizes Mana is immortal and tasers her. Meanwhile Masato's mother, wounded by the Deformed Yukie, tells Yuta that Masato gave her mermaid flesh after a World War II bombing raid, making her essentially his immortal captive. She ran away, but he found her again from the news about the boat accident. She finally dies. Elsewhere, Masato plans to kill Yuta.

Masato tells a captive Mana that he is going to kill Yuta so Mana won't run away. Masato returns to the house, where he tricks Yuta into a booby trap of piano wire, which cuts deeply into Yuta's neck. Masato says that he is over 800 years old and recounts how he used mermaid flesh to make many long-lived companions, all of whom eventually died. Mana escapes and arrives to save Yuta as Masato is beheading Yuta with an ax. Masato shoots Mana, who promises to kill Masato if he kills Yuta. She then collapses. Masato decides Mana is a horrible person and sets fire to the house. Mana awakens in time to drag Yuta's corpse from the fire. Masato drives off in his mother's car, but loses control. As a head-on collision with a truck is imminent, he resolves to find his next companion after he comes back to life. Yuta revives, and Mana cries. Later Yuta asks Mana why she cried when he revived. Mana replies that she was happy.