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Yuki Cross earliest memory is of being attacked by an insane "Level E" type vampire and saved by Kaname Kuran, a pureblood vampire for whom Yuki tries to deal with her seemingly unobtainable love for her hero. Ten years later, Yuki, along with her childhood friend, Zero Kiryu are school guardians at Cross Academy where her adoptive father, Kaien Cross is the headmaster.

Cross Academy is different from any other school. It has a Day Class and a Night Class, with different uniforms and no interaction between these two classes.