The pair were confirmed for the movie earlier this month, making it Sheen's third appearance in the franchise as Tom Logan, following roles in Scary Movie 3 and 4.
Lohan and Sheen will play "the world's hottest new couple", with at least one of them dying in the film's opening sequence, according to The Hollywood Reporter.
The Expendables 2 star Terry Crews has also joined the cast, which already features Ashley Tisdale and Erica Ash.
Scary Movie 5 will be directed by Malcolm Lee and written by David Zucker, with filming due to start in September. The film is expected to open on April 19, 2013.
The comedy is the latest film role for Lohan, who has recently worked on Elizabeth Taylor biopic Liz & Dick and Bret Easton Ellis's new project The Canyons with porn star James Deen.
Sheen currently stars in FX sitcom Anger Management.