Cross Academy is attended by two groups of students: the Day Class and the Night Class. At twilight when the students of Day Class return to their dorm, they cross paths with the Night Class on their way to school. Yuki Cross and Zero Kiryu are the Guardians of the school, protecting the Day Class from the Academy's dark secret: The Night Class is full of vampires!

Yuki Cross has no memory of her past prior to the moment she was saved from a vampire attack ten years ago. She was adopted by the headmaster of Cross Academy, and now works alongside Zero to guard the Academy's secret. Zero Kiryu's family was attacked by a bad vampire four years ago and he was adopted by the headmaster of Cross Academy. Kaname Kuran is a kind vampire who saved Yuki from a bad vampire's attack.