The striker, who is on four bookings for the season so far, is understood to be injured, along with Ashley Young, who misses out entirely.
Javier Hernandez comes in as one of four changes from the 1-1 draw with Swansea as Phil Jones, Nemanja Vidic, Paul Scholes and Ryan Giggs all come in, while Danny Welbeck is absent through illness.
For Newcastle, Gael Bigirimana replaces the suspended Chieck Tiote, with Sylvain Marveaux coming in Jonas Gutierrez in the only other change.
Manchester United starting XI: De Gea, Smalling, Ferdinand, Evans, Evra, Valencia, Carrick, Scholes, Giggs, Van Persie, Hernandez.
Subs: Lindegaard, Vidic, Cleverley, Fletcher, Buttner, Wootton, Tunnicliffe.
Newcastle starting XI: Krul; Coloccini, Santon, Simpson, Williamson; Perch, Anita, Bigirimana; Marveaux, Cisse, Ba.
Subs: Elliot, Tavernier, Ferguson, Obertan, Sammy Ameobi, Campbell, Shola Ameobi.