Nani has been sidelined since the start of November with a hamstring injury and boss Sir Alex Ferguson has revealed the Portugal international should be available again in four or five weeks.
Valencia has a hip injury and will miss Saturday's fixture with the Royals.
Ryan Giggs could be recalled after recovering from a hamstring problem, while fellow veteran Paul Scholes is available following suspension.
Saturday's game comes too soon for defender Nemanja Vidic but Ferguson has confirmed the Serbian may feature against CFR Cluj in the Champions League on Wednesday.
Man United last week