There is a legend in Japan that if one eats the flesh of a mermaid, one will become immortal. This anime recounts the story of Yuhta and Mana, an immortal boy and girl, and their experiences with a family struggling to achieve immortality at any cost.

According to an ancient Japanese legend, mermaid flesh may grant immortality if eaten. However, there is a much greater chance that consumption will lead to death or transformation into a damned creature known as a Lost Soul (or Deformed Ones in the English dub). Mermaid Saga tells the tale of Yuta, an immortal who has been alive for five hundred years, who is wandering across Japan searching for a cure and meeting others whose lives have also been ruined by mermaid flesh in the process.