Karl Robinson makes four changes to the side that was knocked out of Johnstone's Paint Trophy in mid-week.
Defender Tom Flanagan is recalled after serving his one-match suspension for a professional foul and he will partner Shaun Williams in the centre. Alongside those two will be Dean Lewington at left-back and Jon Otsemobor, who missed the trip to Stevenage in mid-week with a groin problem, at right-back.
Elsewhere, the Dons revert back to their familiar two-man midfield partnership of Stephen Gleeson and Darren Potter. The duo will play behind an attacking trio of Daniel Powell, Luke Chadwick and Samir Carruthers, the latter two having been rested on Tuesday night. Up front for the Dons is Patrick Bamford.
Among the replacements for the Dons are Under-18s goalkeeper Charlie Burns and 16-year-old striker Giorgio Rasulo. The two youngsters join Ben Reeves, Alan Smith, Izale McLeod, George Baldock and Jason Banton on the bench.
Leyton Orient: Jones, Omozusi, Vincelot, Cuthbert, Baudry, Cox, James, Lisbie, Mooney, Odubajo, Clarke (c)
Subs: Sawyer, Larkins, Batt, Lee, Lasimant, Bartley, Stockley
MK Dons (4-2-3-1): McLoughlin; Otsemobor, Flanagan, Williams, Lewington (c); Potter, Gleeson; Powell, Chadwick, Carruthers; Bamford.
Subs: Burns (GK), Smith, Reeves, McLeod, Baldock, Rasulo, Banton.