It was reported last year that the fifth 'Underworld' movie would focus on James's vampire character David, who was introduced in 2012's 'Underworld: Awakening'.
But James, 30, who reprises his role as Four in this month's 'Insurgent', said that he is now unlikely to return for the sequel.
"No, they have something in the works, but my involvement in it is... I think it's going be very difficult to do that with these 'Divergent' movies, and my other commitments," James said.
Kate Beckinsale, who has played Selena in all four of the 'Underworld' movies to date, is also expected to be absent from the fifth installment, although writer-producer Len Wiseman recently hinted otherwise.