Manchester United v Manchester City: Predicted lineups
David Moyes has called for his charges to win the Derby, "for the fans," in his pre-match press conference, but there will have to be a lot of work done by the home side for them to ensure they can get a result against their potent rivals.
Losing Robin Van Persie for four to six weeks may not have seemed as such a blow over the weekend as the Red Devils defeated West Ham comfortably at Upton Park, but Manchester City are no West Ham.
The Citizens have the most potent offense in the Premier League if you base that on their goal differential, and with United having shown that they are not up for it against most major competition this season they could be in trouble.
If Moyes' side make a few mistakes early on against City the way they did against Liverpool then if could see a result even more deflating than the 0-3 loss in the Northwest Derby just over a week ago.
Rio Ferdinand could be back despite a nagging injury issue as he will be needed to partner with Phil Jones in the absence of both Johnny Evans and the suspended Nemanja Vidic.
Michael Carrick should be able to return to his normal duties in the holding midfield.
Manchester City is likely to make a few changes as well to their weekend lineup with Edin Dzeko expected to take the place of struggling Alvaro Negredo and Vincent Kompany returns from his suspension just in time to face his rivals.
United XI: De Gea: Rafael, Ferdinand, Jones, Evra; Fellaini, Carrick; Valencia, Mata, Januzaj; Rooney.
City XI: Hart: Zabaleta, Kompany, Demichelis, Clichy; Fernandinho, Toure; Navas, Silva, Nasri; Dzeko.