The Red Devils were left fuming when they were dumped out of the Champions League by Real Madrid following a controversial refereeing incident, which involved the sending-off of winger Nani in the second half.
Meanwhile, the Blues head to Old Trafford on the back of a 1-0 defeat to Romanian outfit Steaua Bucuresti in the first leg of their Europa League round-of-16 tie.
Both sides, who are in contention for two trophies this season, are expected to make changes to their respective teams from midweek, with United striker Wayne Rooney expected to be handed a starting spot following his controversial snub by manager Sir Alex Ferguson against Madrid.
For Chelsea, Demba Ba is expected to assume the role up front following his omission from Thursday night's European fixture due to ineligibility, which is likely to place Fernando Torres on the substitutes bench.
This will be the first time that Rafael Benitez's Blues have played at Old Trafford this season, but they managed to overcome the Red Devils in the Carling Cup at Stamford Bridge following their 3-2 defeat in the Premier League.
Manchester United: LWWWD
Possible starting lineups
Manchester United: De Gea; Rafael, Smalling, Evans, Evra; Cleverley, Anderson; Valencia, Rooney, Kagawa; Hernandez
Chelsea: Cech; Azpilicueta, Cahill, Terry, Cole; Lampard, Ramires; Oscar, Mata, Hazard; Ba
Sports Mole says: 2-1