Ko ljubitelj mastne hrane Frank požre pokvarjeno jajce z virusom Thrax, ga morata rešiti bela krvnička Osmoza Jones in tableta Drix, še preden se ga usodno polasti zlobni Thrax.Potem ko delavec v živalskem vrtu Frank Detorri (Bill Murray) s pokvarjeno hrano zaužije virus Thrax, v njegovem telesu oz. "Frank Cityju" združita moči bela krvnička Osmoza in tableta Drix, da bi virusu preprečila prevzeti "mesto". Da bi stopili na prste Thraxu, mora Osmoza mimo župana Sluzavca pridobiti pomoč njegove asistentke Leah. Ko se Osmoza in Thrax slednjič soočita v spopadu mikrobov, se Frankovo življenje in vsi prebivalci "Frank Cityja" znajdejo v negotovem položaju.
Frank Detomello is a slovenly zoo keeper, and simple father to the only young and bright girl named Shane, who catches a cold right after he swallowed a germ-ridden egg! The inside of his body is known as the "City of Frank". An unlikely hero of a policeman white blood cell, by the name of Osmosis Jones, works as a member of Immunity cell. But with that germ-ridden egg comes a mortal danger: Osmosis discovers Frank has really contracted a villainous and black-hearted deadly virus known as Thrax who arrives and is plotting to ultimately overheat Frank's body, killing him from the inside out! Thrax is motivated by trying to become the nastiest new virus, attempting to kill each new victim faster than the previous. His grandiose plan for Frank is death in 48 hours, breaking previous medical records! Meanwhile the pill that Frank took, Drix arrives in the body and covers Frank's throat with ice to cover the irritation. Osmosis Jones becomes his newest partner. Now it's all up to only Osmosis and Drix to put an end of Thrax's plans before Frank gets sick forever and Shane will become an orphan!