The Blues will be looking to extend their lead over the Red Devils to seven points with a win, but could be affected by a long trip to Donetsk in midweek, where they lost 2-1 to Shakhtar.
Roberto Di Matteo will be without captain John Terry, who will serve the second game in his four-match ban for racially abusing Anton Ferdinand, while Frank Lampard will also miss out due to a calf injury.
United, meanwhile, were forced to come from 2-0 down against Braga in their midweek game, eventually winning 3-2.
Sir Alex Ferguson's men could close the gap on Chelsea to one point, but will have to do so without Shinji Kagawa, who has been ruled out for up to four weeks. Phil Jones and Nemanja Vidic will also be unavailable due to ongoing injury troubles, but Chris Smalling could make a return to the squad.
All eyes will be on the pre-match handshake between the two sides, where it is believed that Rio Ferdinand will shake hands with Ashley Cole, despite the pair being embroiled in a racism row earlier this year.
Man Utd: WWLWW
Possible starting lineups:
Chelsea: Cech; Ivanovic, Cahill, Luiz, Cole; Mata, Ramires, Obi Mikel, Hazard, Oscar; Torres
Man Utd: De Gea; Rafael, Evans, Ferdinand, Evra; Valencia, Carrick, Scholes, Giggs; Van Persie, Rooney
Sports Mole says: 2-2