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!