The Spaniard was absent for Chelsea's 2-1 defeat to Southampton in the Premier League on Saturday due to illness.
Gary Cahill has been ruled out of the clash with a knee injury, while Frank Lampard, John Terry and Fernando Torres have all been handed spots on the bench. Goalkeeper Petr Cech will captain the side at Stamford Bridge.
Meanwhile, there is no place for striker Wayne Rooney in United's squad, while Rio Ferdinand returns to the defensive line following his omission from the Red Devils' 1-0 win over Sunderland in the Premier League on Saturday.
Chelsea starting XI: Cech; Azpilicueta, Ivanovic, Luiz, Cole; Mikel, Ramires; Hazard, Mata, Oscar; Ba
Subs: Turnbull, Terry, Benayoun, Bertrand, Moses, Lampard, Torres
Man United starting XI: De Gea; Jones, Smalling, Ferdinand, Evra; Valencia, Cleverley, Carrick, Nani; Welbeck, Hernandez
Subs: Lindegaard, Giggs, Young, Van Persie, Powell, Kagawa, Vermijl