Since ancient times, the citizens of Salutania have lived within a shroud of miasma, a force that brings forth monsters creating havoc around the world. When the kingdom's Order of Knights becomes incapable of containing the monsters, the Grand Magus summons a holy maiden—the legendary "Saint"—to obliterate the horrid creatures and restore peace. One evening, as Sei Takanashi returns home from a long day at work, a magical force pulls her into a foreign world. Upon her arrival to the kingdom of Salutania, she overhears that the Grand Magus inadvertently summoned two Saints—Sei and a brown-haired girl. Needing only one holy maiden, the prince declares the other girl as the Saint, leaving Sei to her own devices. Sei sets her sight on the Medicinal Flora Research Institute, an establishment known for its studies regarding herbs and potions. While indulging in her latest passion, Sei has a fateful encounter with the commander of the Third Order of Knights. But little does she know, her aptitude as a Saint will continue to exert its influence over her new life.

Dr. Black Jack forgot his doctor's bag, and his assistant (plus self-claimed "wife") Pinoko rushed to deliver the bag but found herself lost in the forest. Guided by a butterfly, she found that many animals in the forest are sick or injured, and Pinoko used her knowledge to help those animals.

The cells of the human body never rest for too long; there's always something new to do and learn every day. At least, that's what Hakkekkyuu U-1146 feels as he rushes to and fro, searching for any pathogens that could cause harm to the body. Despite his dangerous line of work, it's all worth it to protect the happy smiles of Sekkekkyuu AE3803, the platelet crew, his fellow neutrophils, and the other cells he meets along the way. In his latest pathogen-hunting adventures, Hakkekkyuu U-1146 discovers how important cells can sometimes make mistakes, and that not all bacteria are actually bad. Everybody has their bad days, but everything eventually works out when their comrades have their backs. In the end, it's just another normal day for these hardworking cells!

Due to poor lifestyle choices, a certain human's body is in constant turmoil. With germs, bacteria, and foreign substances abound, the jobs of various cells become increasingly difficult and dangerous. As some of the unfortunate ones who matured in this chaotic environment, Sekkekkyuu AA2153 and Hakkekkyuu U-1196 strive to fulfill their duties—even if it means seeing many of their fellow cells lose their lives in duty. Set in an environment vastly different from its parent story, Hataraku Saibou Black portrays the cells' struggles as they try to maintain the body's health. However, the human's condition continues to deteriorate, and whether or not these efforts will amount to something concrete depends on the cells!