Javier Hernandez takes the place of the Dutch striker, who is not even among the substitutes at Old Trafford.
Manager David Moyes told Sky Sports News: "He has two bad toes and has been complaining about his groin so we took the chance to rest him and get him ready for the weekend."
For the visitors, captain Xabi Prieto continues his comeback from injury to take his place in midfield, while former Arsenal man Carlos Vela will want to impress on his return to England.
Man Utd: De Gea, Rafael, Jones, Evans, Evra, Valencia, Carrick, Giggs, Kagawa, Rooney, Hernandez
Real Sociedad: Bravo, C. Martinez, Mikel, Inigo, De la Bella, M. Bergara, Zurutuza, X. Prieto, Vela, Seferovic, Griezmann