Inside the human body, there are around thirty-seven billion cells, who diligently carry out their duties every day. New to her job, clumsy but cheerful Sekkekkyuu AE3803 is excited to start delivering oxygen and collecting carbon dioxide despite her poor sense of direction. Meanwhile, Hakkekkyuu U-1146 is always ready to fight and kill any pathogen that he comes across. After running into each other multiple times, they quickly become good friends, regardless of their contrasting personalities.

Entertaining and educational, Hataraku Saibou follows the two blood cells and their many comrades as they work together to keep the body healthy.