Chris Smalling will be handed his first start in a Manchester derby.
Rio Ferdinand (calf) and Jonny Evans (ankle) are both ruled out, meaning Smalling will partner Nemanja Vidic in the centre of United's defence.
Javier Hernandez was the latest member of the Red Devils' international contingent to report back for duty, although given his arduous journey following Mexico's meeting with Bosnia, the best he can hope for is a place on the bench.
Manchester City midfielder Nigel De Jong is doubtful for the derby against because of an ankle injury.
However defender Micah Richards has recovered from a similar problem and comes into contention at Old Trafford.
Striker Mario Balotelli could return after a four-week absence with a knee injury which followed his hat-trick against Aston Villa.
United (from): Van der Sar, Lindegaard, Kuszczak, Rafael, O'Shea, Brown, Smalling, Vidic, Evra, Fabio, Nani, Fletcher, Carrick, Scholes, Gibson, Anderson, Park, Bebe, Giggs, Rooney, Berbatov, Hernandez, Owen.
City (from): Hart, Given, Zabaleta, Richards, Boateng, K Toure, Kompany, Boyata, Kolarov, Lescott, Wright-Phillips, De Jong, Vieira, Milner, Y Toure, Silva, Barry, Tevez, Dzeko, Balotelli, Jo, Guidetti.