Patrice Evra returns to the United line-up for the visit of Spurs after missing the season-opening win at West Brom with an ankle injury.
With Rio Ferdinand unlikely to return until next weekend due to a hamstring injury, and with captain Nemanja Vidic out for up to five weeks with a calf problem, youngsters Phil Jones and Jonny Evans will form the centre-back pairing.
Darren Fletcher (virus), Antonio Valencia (ankle) and Javier Hernandez (concussion) are all closing in on a return, but are not yet ready.
Michael Owen is out with a back problem, whilst Rafael faces up to 10 weeks on the sidelines after undergoing surgery to repair a dislocated shoulder.
Luka Modric is likely to return to Tottenham's starting line-up after missing the 5-0 Europa League win over Hearts with a minor groin injury.
Tom Huddlestone (ankle) could also return after starting on the bench at Tynecastle, but fellow midfielders Sandro, Wilson Palacios (both knee) Steven Pienaar (groin), and Jermaine Jenas (Achilles) are all out.
Peter Crouch will be tested over the weekend after missing Thursday's win with an ankle injury but Ledley King and Alan Hutton are sidelined with knee injuries and William Gallas is also out with a calf problem.
Manchester United (from): De Gea, Lindegaard, Smalling, Ferdinand, Jones, Evra, Evans, Fabio, Nani, Park, Cleverley, Anderson, Carrick, Giggs, Young, Rooney, Berbatov, Welbeck, Diouf, Macheda.
Tottenham (from): Gomes, Friedel, Cudicini, Bale, Kaboul, Bassong, Dawson, Corluka, Walker, Assou-Ekotto, Huddlestone, Lennon, Van der Vaart, Modric, Kranjcar, Rose, Livermore, Townsend, Bentley, Pavlyuchenko, Crouch, Defoe.