Keisuke Sannan serves as a Vice-Commander of the Shinsengumi alongside Hijikata Toshizo, reporting to Commander Isami Kondou. Hailing from Edo, he functions as the group's consultant and chief strategist, leveraging his intellect and education to devise tactics. His scholarly demeanor is accentuated by distinctive round glasses and dark brown, shoulder-length hair, typically slicked back with a single lock of bangs framing his face. He favors a dark green kimono shirt paired with a dark blue vest and black pants, later adopting a dark Western-style uniform featuring vinous and yellow accents. Post-transformation into a Rasetsu, his hair turns silver and his eyes glow red.

Initially presenting a polite and amiable facade, Sannan harbors underlying cynicism and resents pity. He holds deep loyalty to the Shinsengumi and his comrades, especially respecting Hijikata despite occasional clashes. A severe injury to his sword arm during an Osaka battle drastically alters him. The loss of his swordsmanship fuels profound self-loathing, bitterness, and withdrawal from others, worsened by Itou Kashitaro's arrival and subsequent undermining of Sannan's position. He grows secretive and hypersensitive to perceived slights.

Desperate to regain his value, Sannan secretly researches the Ochimizu (Water of Life), an elixir created by Chizuru Yukimura's father that transforms humans into Rasetsu—beings granted enhanced strength and regeneration but cursed with bloodlust and shortened lifespans. After refining the formula, he consumes it. The initial transformation causes him to attack Chizuru before regaining control. He establishes the Rasetsu Corps within the Shinsengumi, advocating its use despite internal concerns about madness and uncontrollable urges.

Leading the Rasetsu Corps intensifies Sannan's research obsession, particularly after discovering Chizuru's demon blood can stabilize Rasetsu. This drives him to attempt extracting her blood for experiments, an act intercepted by Hijikata. Rumors link him to civilian killings, later revealed as the elimination of individuals surveilling Chizuru under orders from the demon Kaoru. Following the Shinsengumi's defeat at Toba-Fushimi, Sannan departs for Sendai, appearing to defect to Koudou Yukimura's faction. His true mission is infiltration to gather research on reversing the Rasetsu condition. During the Sendai Castle confrontation, he betrays Koudou, aiding the Shinsengumi to destroy the assembled Rasetsu forces, declaring their existence unsustainable due to rapid physical decay and uncontrollable bloodlust.

Sannan's physical deterioration accelerates from using his Rasetsu powers, manifesting as body cracks and disintegration into ash. He meets his end alongside Heisuke Toudou at Sendai Castle, his body consumed by blue flames—the common Rasetsu fate. In the Tsukikage no Shou OVA, set after Koudou's defeat, Sannan and Chizuru journey to Europe seeking a Rasetsu cure, encountering reports of similar entities called vampires. They continue research in France, sustained by a special serum slowing his corruption. During this time, Sannan reflects that becoming a Rasetsu, despite the cost, enabled him to protect those he valued.

The spin-off Hakuouki SSL presents an alternate universe where Sannan serves as school nurse at Hakuo Academy, free from his injury and Rasetsu transformation. Here, he exhibits a reserved yet kind and observant nature, gradually forming a bond with Chizuru. While other characters mention a "dark side," this setting focuses on his gentle interactions and subtle romantic developments with Chizuru through her graduation, leaving that aspect unexplored.

Across all portrayals, Sannan's arc traces his struggle for purpose after losing his swordsmanship, his morally ambiguous choices to regain agency via the Ochimizu, and his ultimate redemption through sacrifices protecting the Shinsengumi and its members. His relationship with Chizuru acts as a stabilizing force, anchoring his humanity and values amidst his obsessive descent.