Sir Alex Ferguson will dig deep into his squad as Manchester United look to overcome the challenge of the non-leaguers.
With Rio Ferdinand and Jonny Evans ruled out and Nemanja Vidic likely to be rested, Wes Brown or John O'Shea will probably fill a central defensive berth.
Anders Lindegaard or Tomasz Kuszczak will replace Edwin van der Sar in goal, whilst Javier Hernandez, Gabriel Obertan and Bebe can all expect to play a part.
Crawley Town midfielder Scott Neilson will be absent after he failed to recover from a foot injury.
Pablo Mills was rested for Tuesday's 0-0 draw against Wrexham but is expected to return to the starting XI at Old Trafford.
Defender John Dempster and midfielder Josh Simpson are cup-tied having played in previous rounds for Kettering and Southend respectively.
Man Utd (from): Lindegaard, Kuszczak, Rafael, O'Shea, Brown, Smalling, Vidic, Evra, Fabio, Obertan, Bebe, Nani, Gibson, Scholes, Fletcher, Anderson, Carrick, Giggs, Berbatov, Rooney, Hernandez.
Crawley (from): Kuipers, Rusk, Wilson, Shearer, Rents, Mills, Howell, McFadzean, Hunt, Smith, Torres, Bulman, Dance, Gibson, Tubbs, McAllister, Cook, Brodie, Masterton.