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)