Conan O'Brien was a host of Late Night with Conan O'Brien, with co-host Andy Richter and band leader was Max Weinberg from 1993 to 2009, before moving on to The Tonight Show With Conan O'Brien for seven months, before a controversy that resulting in him leaving NBC, and Jay Leno taking back The Tonight Show. As of 2015 Jimmy Fallon is the current host of The Tonight Show.
O'Brien appeared in the film, South Park: Bigger, Longer & Uncut, in which he hosted guests Brooke Shields and Terrance and Phillip, before tricking Terrance and Phillip into being captured by Sheila Broflovski and Mothers Against Canada to be executed. Feeling guilty for betraying them, he commits suicide by jumping out a window. Despite Kenny's wish, he can be seen in Hell briefly in "Do the Handicapped Go to Hell?"'.
He appeared yet again, though without lines, in "Funnybot" though he can barely be seen in the final episode, as one of the out-of-work comedians holding up the school.
In South Park: Bigger, Longer & Uncut, Conan O'Brien wears a green suit and a blue neck tie. He has wavy red hair, red eyebrows, and has no other facial hair. In "Fishsticks", he wore a black suit with a black tie. In his redesign, his wavy red hair is more detailed and he retains his red eyebrows, albeit with more detail. Conan's redesign resembles himself more than the original design as seen in the film.
- The voice of Conan O'Brien in the film was performed by actor Brent Spiner, best known for his role as Data from Star Trek: The Next Generation. Spiner confirmed on Twitter he did not return for "Fishsticks".
- Conan O'Brien was originally meant to kill himself with a gunshot to the head in South Park: Bigger, Longer & Uncut instead of jumping out of the window to his death, but the MPAA rejected the original scene on basis of the gun violence since Columbine High School massacre, so it was switched out with the scene in which O'Brien jumps and falls to his demise.
- In an unofficial short involving O'Brian going to the Emmy Awards, Conan can be seen locking himself in Stan Marsh's closet, a nod to the episode, "Trapped in the Closet".
- "South Park: Bigger, Longer & Uncut" - Helps the Mothers Against Canada kidnap Terrance and Phillip, then shortly after, he commits suicide by jumping out of a window.
- "Do the Handicapped Go to Hell?" - Appears briefly in Hell.
- "Fishsticks" - Introduces Carlos Mencia on Late Night.
- "Funnybot" - Appears as one of the out-of-work comedians holding up the school.