Second string players Gabriel Obertan, Bebe and Darron Gibson could all be handed a run out by manager Sir Alex Ferguson.
Next week's Champions League engagement with Marseille should see top line stars, such as Nemanja Vidic, Dimitar Berbatov and Patrice Evra, taken out of the firing line.
Guaranteed to miss the game are Jonny Evans (ankle), Rio Ferdinand (calf), Park Ji-Sung (hamstring) and Owen Hargreaves (hamstring). Michael Owen (groin) joined the injured list this week after he pulled up in training.
Despite his return to training with the reserves, Antonio Valencia is still a few weeks short of a return from a broken leg and dislocated ankle.
Youngsters Joshua King, Matthew James, Ravel Morrison and Will Keane could be handed spots on the substitute's bench.
Possible starting XI: Lindegaard; O'Shea, Smalling, Brown, Fabio; Gibson, Carrick, Anderson; Bebe, Hernandez, Obertan.
Boss Steve Evans has a near fully-fit squad to choose from for the visit to Old Trafford. After being rested for Tuesday's 0-0 draw with Wrexham, goalkeeper Michael Kuipers, midfielders Sergio Torres and Ben Smith, plus striker Craig McAllister should all return.
Defender Dean Howell and midfielder David Hunt both shook off knocks to feature in that match. Only Scott Neilson (broken toe) is set to miss out.
Possible starting XI: Kuipers; Dempster, Wilson, Howell, McFadzean; Smith, Torres, Mills, Gibson; Tubbs, McAllister.
Second-string's time to shine
Redemption has arrived for Ferguson's reserves stars after their embarrassing FA Cup third round exit to Leeds United last term.
Players such as Wes Brown and Gabriel Obertan barely got another look in after the Scot fell foul to the first giant-killing of his long United reign thanks to Jermaine Beckford's goal.
United's squad seemed incredibly thin on the ground then, with a similar tale repeated in this season's League Cup defeat to West Ham. With Ferguson reputed to be ready to wield the axe in the summer, several men are guaranteed to be fighting for their Old Trafford futures on Saturday evening.
From Blue Square to the big time
Even the ambitious owners of Crawley Town couldn't have envisaged a trip to Old Trafford so soon into their project to transform the Sussex side.
Money has been pumped in at a scale that has drawn envious eyes even from League One outfits. This splurge has seen league football just a step away for the first time in the club's existence.
The third round slaying of Derby County stole the headlines. A victory against the Premier League leaders will dominate the history books of the oldest association football competition in the world.