The Milton Keynes club, in the fourth round for the first time in their short history, will definitely be without cup-tied striker Izale McLeod and injured midfielders Stephen Gleeson (broken foot) and Luke Chadwick (knee).
Boss Karl Robinson also has concerns over the fitness of leading scorer Dean Bowditch and midfielders Daniel Powell and Ryan Harley.
Ahead of the tie at Loftus Road, Robinson said: "We'll be down to the bare bones. We're going to be without four or five key players, but we've been used to that in recent weeks and we're looking forward to the challenge."
However, Robinson's midfield options have been boosted by the loan arrival of Chris Lines and the Sheffield Wednesday player is likely to make his Dons debut against the Premier League club.