Chris Rock

Osmosis Jones (voice)

Laurence Fishburne

Thrax (voice)

David Hyde Pierce

Drix (voice)

Brandy Norwood

Leah (voice)

Elena Franklin

Shane Detorre

Bill Murray

Frank Detorre

William Shatner

Mayor Phlegmming (voice)

Ron Howard

Tom Colonic (voice)

Kid Rock

Kidney Rock (voice)

Molly Shannon

Mrs. Boyd

Chris Elliott

Bob

Jonathan Adams

Officer Tom (voice)

Carlos Alazraqui

Spanish Germ (voice)

Keith Anthony

Additional Character Voices (voice)

Eddie Barth

Conductor (voice)

Sally Brooks

Additional Character Voices (voice)

Rodger Bumpass

Joe Cramp / Announcer for Nerve News Network (voice)

Michael Carven

Additional Character Voices (voice)

Paul Christie

Dan Matter / Germ (voice)

Janis Dardaris

Additional Character Voices (voice)

Wendy Dillon

Additional Character Voices (voice)

Antonio Fargas

Chill the Flu Shot (voice)

Eddie Frierson

Frank Police Department Officer (voice)

Donald Fullilove

Doughnut (voice)