 Chris RockOsmosis Jones (voice) | Osmosis Jones (voice) |
 Laurence FishburneThrax (voice) | Thrax (voice) |
 David Hyde PierceDrix (voice) | Drix (voice) |
 Brandy NorwoodLeah (voice) | Leah (voice) |
 Elena FranklinShane Detorre | Shane Detorre |
 Bill MurrayFrank Detorre | Frank Detorre |
 William ShatnerMayor Phlegmming (voice) | Mayor Phlegmming (voice) |
 Ron HowardTom Colonic (voice) | Tom Colonic (voice) |
 Kid RockKidney Rock (voice) | Kidney Rock (voice) |
 Molly ShannonMrs. Boyd | Mrs. Boyd |
 Chris ElliottBob | Bob |
 Jonathan AdamsOfficer Tom (voice) | Officer Tom (voice) |
 Carlos AlazraquiSpanish Germ (voice) | Spanish Germ (voice) |
| KKeith AnthonyAdditional Character Voices (voice) | Additional Character Voices (voice) |
 Eddie BarthConductor (voice) | Conductor (voice) |
 Sally BrooksAdditional Character Voices (voice) | Additional Character Voices (voice) |
 Rodger BumpassJoe Cramp / Announcer for Nerve News Network (voice) | Joe Cramp / Announcer for Nerve News Network (voice) |
| MMichael CarvenAdditional Character Voices (voice) | Additional Character Voices (voice) |
| PPaul ChristieDan Matter / Germ (voice) | Dan Matter / Germ (voice) |
 Janis DardarisAdditional Character Voices (voice) | Additional Character Voices (voice) |
| WWendy DillonAdditional Character Voices (voice) | Additional Character Voices (voice) |
 Antonio FargasChill the Flu Shot (voice) | Chill the Flu Shot (voice) |
| EEddie FriersonFrank Police Department Officer (voice) | Frank Police Department Officer (voice) |
 Donald FulliloveDoughnut (voice) | Doughnut (voice) |
 Jackie GonneauAdditional Character Voices (voice) | Additional Character Voices (voice) |
| SShannon GregoryAdditional Character Voices (voice) | Additional Character Voices (voice) |
 Richard Steven HorvitzAdditional Character Voices (voice) | Additional Character Voices (voice) |
 Rif HuttonCharlie (voice) | Charlie (voice) |
| AArt KimbroAdditional Character Voices (voice) | Additional Character Voices (voice) |
| JJoyce KurtzAdditional Character Voices (voice) | Additional Character Voices (voice) |
