Alcohol, smoking, and stress—in the body subjected to these irritants, the cells responsible for maintaining life seem to fight a war that never ends. Due to a severe shortage of workers, Red Blood Cell AA2153 has to quickly learn to deliver oxygen and collect carbon dioxide, even in dangerous conditions. Meanwhile, White Blood Cell U-1196 has to do her part by dealing with germs and viruses during life-threatening situations. In the midst of these crises, they have to work together to keep the body healthy, despite not knowing if their sacrifices will be worthwhile. Cells at Work! Code Black takes a different approach by showing the grittier side of the jobs our cells perform.

Two realms exist in the ancient land of Yanato: the Lofty Realm, where gods reside, and the Lowly Realm, where humans reside. Princess Sakuna was the daughter of the god of war and goddess of harvest, but she led a lazy life. One day, she is banished to Hinoe Island, the Isle of Demons. Stranded in a barren land, Sakuna sets out to slay demons and farm rice. Her new adventure begins!