The story revolves around the main character, Karin, the middle child in a family of vampires who immigrated to Japan two centuries earlier. However, Karin is different from the rest of the family in that she produces blood instead of feeding on it; because of this, she has to inject blood by biting someone or else she suffers exaggerated nosebleeds. Because of her unusual condition, Karin lives her life just as an ordinary teenage girl would, despite being considered something of a freak by her family. She is able to venture outside during the day and attend high school, and follows the sleep pattern of normal humans. However, the general peacefulness of her life is disrupted with the arrival of a new transfer student, Kenta Usui.
Any time she goes near him her blood increases. At first she tries to avoid him but it doesn't work since they are in the same class and work in the same restaurant. Kenta begins to think that there is something fishy about Karin and eventually he learns her secret. Karin's elder brother Ren tries to erase his memory but Anju, Karin's younger sister stops him from doing so. She also convinces their parents Henry and Calera to make Kenta their ally, because he can help Karin during the daylight. Karin and Kenta become friends. Kenta helps Karin clean up the mess made by her nosebleeds and Karin prepares him a lunch box (bento) every day.
As the story progresses Kenta and Karin's attachment to one another grows, and so do their problems. First Karin's grandmother Elda breaks free from her coffin (which Calera had sealed her into) and starts wrecking everyone's lives. Except for her bust size, hair length, and hair color she looks identical to Karin, and uses this resemblance to go unnoticed in Karin's school.
She attempts to drink Kenta's blood because she believes humans and vampires cannot coexist. Eventually, she gives up and returns to her casket.
In the anime adaptation, an additional character, Winner Sinclair, is added to the series. Winner is a vampire hunter who falls in love with Karin, while Karin's best friend Maki Tokito falls in love with him.