After getting home at dawn, thirteen year old girl Sumiko Kamado discovers her middle aged parents Tanjuro and Kie and younger siblings, twelve year old triplets Nezuko, Takeo and Hanako, eleven year old boy Shigeru and ten year old boy Rokuta, had all been turned into demons with a immunity to the sunlight and their memories intact the night before. Shortly after this, the family of eight is found by a samurai who captures them and sends them to the entertainment district of Tokyo. Due to her family having been turned into demons, the teen girl is employed into the district's Tokito house alone. Two years later, Sumiko, now fifteen, is found there by male demon slayers Tengen Uzui and Kyojuro Rengoku. They go upstairs to the large room she had been sharing with her family just before Tanjuro, Kie, Nezuko, Takeo, Hanako, Shigeru and Rokuta wake up from the comatose states they had been in for a year.
Sakura Hirai is a 20 year old girl who lives down the mountain from the Kamado family where she has looked after their children for years after the Father of the Kamado family, Tanjuro fell ill. Sakura's responsibilities consisted of looking after the younger children and helping the older children, Tanjiro and Nezuko descend the mountain day after day to go work in the village. As the village's doctor, Sakura was always busy and is very skilled in care.
After a fateful night where Sakura and Tanjiro didn't return to the family's cabin, Tanjiro, the eldest son of the Kamado family, comes home to find his entire family slaughtered. Tanjiro, in a complete panic checks on the oldest sister first, Nezuko, who is still warm and rushes her down the mountain to see Sakura who seems calm about the whole situation. After checking Nezuko's injuries, the three return to the household where Sakura and Tanjiro bury the family's corpses before heading off.
But Nezuko is not herself anymore as she starts to turn into a bloodthirsty rampaging demon on the back of her loving brother and threatens to attack, Sakura turns to the only thing she knows best, protecting those she holds close.