It centers on Osmosis "Ozzy" Jones, a cheeky-chappy white blood cell, and Drix, a level-headed cold pill, who battle germs and viruses inside the body of teenage boy Hector Cruz.

After defeating the bacterium and settling into their new home, Ozzy and Drix are hired as private investigators, vowing to protect Hector's health and guide him through the misadventures of adolescence.

Fox), an attorney at law who helps cells find homes in Hector, and who becomes Ozzy's new love interest to replace Leah Estrogen after forever leaving her and Frank; and the Brain Cell Advisors (voiced by Pat Fraley), advisors who help Mayor Spryman run the city due to Spryman being incompetent in his job.

Unlike the original film it was spun-off from, Ozzy & Drix was entirely animated and contained no live-action scenes while being considered in its own continuity as this version of Frank DeTorre is still in bad shape.

In multiple episodes, producer Ron Myrick integrated stock footage from the original film such as the human body's traffic, the inside of the mouth, and the dam bursting in the runny nose.