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The Vampire Knight manga series and its anime adaption features a relatively small cast of characters created by Matsuri Hino. The series takes place in an alternative future of earth where global warming occurred ten thousand years ago giving rise to immortal vampires and dramatically reducing the number of humans. Their opponents, the vampire hunters were borne of a necessity for humans to defend themselves against the vampires who were turning their kind into the slave army. In spite of being set in future earth, it features a mixture of contemporary and old fashioned technology.

The primary character and heroine of the series is Yuuki Cross, a naive but energetic human, who is the introductory narrator, she is supported by childhood friend and vampire hunter Zero Kiryuu and her crush Kaname Kuran. The story is set in a school environment and originally the cast is divided into human and vampire students, but after the main three characters are eventually revealed to be vampires, the story moves away from the school environment in the second arc. Zero Kiryuu’s revelation as a vampire drives the first half of the first arc and the second half is driven by Yuuki’s revelation to be a vampire. In spite of the secrets held by the two former humans, Kaname is the character with the most secrets, which appear to be the focus of the beginning of the second arc.

While initially developing the characters, Hino reported that though Kaname was created earlier, at every step in the characters' creations, she found it difficult to maintain a balance between Kaname and Zero as she struggled with fears of the former overshadowing the latter.

is the adopted daughter of the headmaster of Cross Academy, a 16 year old first year student who wields the Artemis staff, an anti-vampire weapon formerly used by her mother. She begins as a human, a Guardian protecting the human students from the vampire students. Yuuki is close friends with Zero Kiryu, who she becomes determined to help once she discovers he had been turned into a vampire, following which their friendship rapidly evolves. She has been in love with Kaname Kuran, a pureblood vampire, since he saved her as a young child, but her affection is later divided to include Zero as well. She is generally a kind, caring, cheerful, and comedic character, but often portrayed as not being very smart, being a poor student due to the fact that she is a guardian at night and student in the daytime, giving her little time to study and sleep. She is often kept ignorant by other characters who know more about goings-on, which results in her character feeling guilty for being unaware of the suffering of other characters. Hino Matsuri has described Yuuki as a healing and soothing character, who exemplifies her justice side.

Zero Kiryuu has not been a contender in any CBUB matches.