Anime based upon the original Argentine graphic novel series of the same name. The story follows the titular character who is a genetically engineered super-soldier; one of the creations of Dr. Von Reichter's diabolic experiments. (The fictional) Von Reichter is actually a former Nazi who conducted horrendous experiments during the second world war. He flees to South America where he continues his experiments which culminate in the creation of the "Cybers," one of which happens to be Cybersix. However, since the Cybers exhibit free will at an young age (an undesired trait), Von Reichter destroys all the Cybers to prevent a rebellion. In the present day, Cybersix is one of the Cybers who managed to escape and is living a quiet life under the alias of "Adrian Seidelman"; however, she finds out that her survival is dependent on a special substance that Von Reichter created and thus she is forced to hunt down the "Technos," a newer generation of super-soldiers created by him, in order to survive. Unintentionally, in the process, Cybersix becomes a superhero protecting the world from Dr. Von Reichter's creations and his evil plans.

Tomoya Okazaki is a cynical delinquent who lacks ambition as he apathetically labors through high school. During his childhood, a tragedy had caused his father to seek solace in alcoholism and neglect his son. Yet, meaningful human interaction can be a benediction, as Tomoya learns when he meets the enigmatic Nagisa Furukawa. The odd girl offers a gesture of friendship to Tomoya, but he rejects the request, dismissing it as a trivial incident. However, as he soon realizes that he is encountering Nagisa more and more often during school, Tomoya drops his discompassions and befriends the girl. When he learns that Nagisa's dream is to revive the Drama Club, Tomoya decides to shed his detachment from the ordinary pleasures of life and dedicate himself to helping his new friend achieve her ambition. But what starts as a simple friendship may progress into something far more deep, intimate, and life-changing. As the pair face various hardships and afflictions, Tomoya and Nagisa gradually come to terms with the challenges of life. [Written by MAL Rewrite]

In a world where dead people turn into books and are stored in the Bantorra Library where anyone who reads a book can learn their past, Bantorra Library is maintained by Armed Librarians who wield psychic powers and their enemy is a religious society known as Sindeki Kyoudan.

Episode 0, consisting of two subepisodes: "Sekirei Shindan" (鶺鴒診断) and "Sekirei Yoka" (鶺鴒余暇), of Sekirei: Pure Engagement included on the first DVD/BD volume.