Smalling was forced off the pitch for England in midweek and has failed to recover.
Angel Di Maria and Radamel Falcao were once again forced to settle for a place on the bench.
Tim Sherwood was forced to make three changes with Tom Cleverley ineligible to play against his parent side.
De Gea, Valencia, Jones, Rojo, Blind, Carrick, Herrera, Mata, Fellaini, Young, Rooney.
Valdes, Rafael, McNair, Pereira, Januzaj, Di Maria, Falcao
Guzan, Hutton, Okore, Clark, Lowton, Delph, Sanchez, N’Zogbia, Weimann, Agbonlahor, Benteke.
Given, Vlaar, Bacuna, Cole, Gil, Baker, Grealish
