In the tumultuous aftermath of poor lifestyle choices, a human body descends into constant chaos, besieged by germs, bacteria, and foreign invaders. Amidst this turbulent environment, Sekkekkyuu AA2153 and Hakkekkyuu U-1196, products of unfortunate maturation within the chaos, valiantly carry out their duties despite the perilous challenges that surround them. Their commitment to maintaining the body's health leads them through a harrowing journey, witnessing the sacrifice of many fellow cells in the line of duty.

Set against a backdrop vastly distinct from its predecessor, Hataraku Saibou Black unfolds the gripping narrative of cells grappling with the relentless struggle to preserve the deteriorating state of the human body. As the condition worsens, the fate of these dedicated cells hangs in the balance, and the question remains: can their efforts yield tangible results in the face of such adversity?