The interior shots of Molly and Carl's house are filmed on the set of Hope and Michael Steadman's house from Thirtysomething (1987). The exterior is the house used at the end of 13 Going on 30 (2004), where it is pink.
The three main stars of the film, Owen Wilson, Kate Hudson, and Matt Dillon all have the same amount of letters in their first names (four) and last names (six). All three stars are left-handed as well.
The cover for Dupree's book, "Seven Different Kinds of Smoke", exactly mimics the cover for Lance Armstrong's book, "It's Not About the Bike", which is mentioned a couple of times in the movie. Dupree reads Lance's book, and at the end, Lance reads Dupree's book.
Donald Fagen and Walter Becker, of the popular 70's band "Steely Dan", addressed a letter to Owen Wilson's brother, Luke, on their blog with claims that the idea of "You, Me and Dupree" was stolen from their song, "Cousin Dupree". (Lyrics to "Cousin Dupree" can also be found on their website.) Only the name Dupree, and the possibility that Cousin Dupree and that Wilson's character Dupree both may have slept on a couch seem to be the only common links in their claims.
Lance Armstrong: who is Dupree's inspiration, makes three cameos in the movie. First, he is seen in the biking video, to which Dupree exercises (despite appearances, this is not stock footage, but filmed specifically for this movie). Second, he appears in the dream sequence, where Carl imagines Dupree and Molly on Bob's boat (Armstrong is wearing Dupree's "Say Hello to my little friend" gnome shirt). Finally, in a brief after-the-credits scene, he is shown reading Dupree's book, in exactly the same way that Dupree was seen earlier reading Armstrong's book.