Chris Rock as Osmosis Jones (voice)

Laurence Fishburne as Thrax (voice)

David Hyde Pierce as Drix (voice)

Brandy Norwood as Leah (voice)

Elena Franklin as Shane Detorre

Bill Murray as Frank Detorre

William Shatner as Mayor Phlegmming (voice)

Ron Howard as Tom Colonic (voice)

Kid Rock as Kidney Rock (voice)

Molly Shannon as Mrs. Boyd

Chris Elliott as Bob

Jonathan Adams as Officer Tom (voice)

Carlos Alazraqui as Spanish Germ (voice)

Keith Anthony as Additional Character Voices (voice)

Eddie Barth as Conductor (voice)

Sally Brooks as Additional Character Voices (voice)

Rodger Bumpass as Joe Cramp / Announcer for Nerve News Network (voice)

Michael Carven as Additional Character Voices (voice)

Paul Christie as Dan Matter / Germ (voice)

Janis Dardaris as Additional Character Voices (voice)

Wendy Dillon as Additional Character Voices (voice)

Antonio Fargas as Chill the Flu Shot (voice)

Eddie Frierson as Frank Police Department Officer (voice)

Donald Fullilove as Doughnut (voice)

Jackie Gonneau as Additional Character Voices (voice)

Shannon Gregory as Additional Character Voices (voice)

Richard Steven Horvitz as Additional Character Voices (voice)

Rif Hutton as Charlie (voice)

Art Kimbro as Additional Character Voices (voice)

Joyce Kurtz as Additional Character Voices (voice)

Anne Lockhart as Female Red Blood Cell (voice)

Sherry Lynn as Trudy (voice)

Danny Mann as Musician Cell (voice)

Mickie McGowan as Brain Librarian (voice)

Kenny Olson as Kidney Rock Band (voice)

Jason Krause as Kidney Rock Band (voice)

Joe C. as Kidney Rock Band (voice)

Stefanie Eulinberg as Kidney Rock Band (voice)

Jimmie Bones as Kidney Rock Band (voice)

Uncle Kracker as Kidney Rock Band (voice)

Joel Silver as Police Chief (voice) (uncredited)

David Ossman as Scabies (voice) (uncredited)

John Melendez as Artie (voice)

Héctor Mercado as Additional Character Voices (voice)

Paul Pape as Male Red Blood Cell #2 (voice)

Marilyn Pasekoff as Additional Character Voices (voice)

Chris Phillips as Firefighter Doug (voice)

Lynne Redding as Additional Character Voices (voice)

Al Rodrigo as Frank Police Department Walkie Talkie (voice)

Herschel Sparber as Bruiser (voice)

Doug Stone as Police Officer Jamie (voice)

Steve Susskind as Mob Boss Germ (voice)

Keri Tombazian as Additional Character Voices (voice)

Paul Tuerpe as Additional Character Voices (voice)

Robert Wisdom as Big Germ (voice)

Danny Murphy as Zookeeper Superintendent

Jack McCullough as Zookeeper

Will Dunn as Oyster Boy

Jackie Flynn as School Janitor

Kelsey Jordan as Bus Girl #1

Abe Farrelly as Bus Girl #2

Jesse Peter as Laughing Boy

John-Eliot Jordan as Pea Soup Manager

Nancy Byers as Pea Soup Supervisor

Kevin J. Flynn as Docky's Clamshack Waiter

Sean Gildea as Dreamy Photographer

Kathryn Frick as Nurse #1

Nikki Tyler-Flynn as Nurse #2

Elizabeth Jordan as Nurse #3

Zen Gesner as ER Doctor #1

Marc Hyman as ER Doctor #2

Zak Penn as ER Doctor #3

Diane Conrad as Zoo Visitor or Staff

Judith Conrad as Zoo Visitor or Staff

Thomas Jordan as The Zoo Visitor or Staff

Sydney J. Bartholomew Jr. as Zoo Visitor or Staff

Erica Johnson as Zoo Visitor or Staff

Bo Cleary as Pea Soup Staff

Bruce McIntyre as Pea Soup Staff

Colleen O'Donnell as Docky's Clamshack

Docky as The Bikini Gang

Joe Murphy as The Bikini Gang

Brian Mone as Police Officer

Sean Fitzgerald as Police Officer

Grace Costa as ER Nurse

Emily O’Donnell as School Girl