Bill Murray's character mentions a "National Chicken Wing Festival" in Buffalo, New York. While the festival did not exist during the filming of the movie, this mention caused organizers to create an annual festival in Buffalo. The festival has been held annually on Labor Day weekend since 2002.
At 01:01:04 into the movie, Osmosis Jones walks into the Chief's office and says "Brandy! I mean, Leah. Why are you here?" He is speaking to the mayor's aide Leah, who is voiced by Brandy Norwood. Chris Rock unintentionally ad-libbed that line and the filmmakers decided to put it in.
In the original script and in early cuts of the film, a scene was featured when Osmosis and Drix go to the Gonad's Gym. It involved them talking to the "exercising" sperm cells. The scene was cut in order to stay family friendly. The Gonad's Gym logo does appear on Drix's suitcase during a scene in police station locker room.
The population of the City of Frank is 78,899,293,934,872,302,829,287,438.
David Hyde Pierce was hired for the role of Drix because he was "the whitest white man" they could find.