Man Utd's Zlatan Ibrahimovic is suspended, while Wayne Rooney, Anthony Martial and Marcus Rashford are all out of the FA Cup quarter-final trip to Chelsea on Monday night.
Ibrahimovic, who assisted United's goal in their 1-1 Europa League draw against Rostov on Thursday, received the suspension after the FA took retrospective action for his elbow on Tyrone Mings against Bournemouth.
Rooney is believed to have been involved in an accidental training ground collision with defender Phil Jones, while Martial will also miss the match through injury.
Academy graduate Marcus Rashford, who has scored three goals in two FA Cup appearances this season, is absent through illness.
Chelsea head coach Antonio Conte, meanwhile, refuses to be distracted by the mind games deployed by managerial rivals including Jose Mourinho, saying talking does not win games.
Conte said: "I'm very focused on the pitch. The mind games don't bring you to win, above all if you face a team who is focused."
The Blues will have had a full week of rest by kick-off on Monday night, while Mourinho could make changes with the match falling in between the two legs of their Europa League last-16 tie.
Team news
Conte has a fully-fit squad and is considering his options for the match.
Chelsea captain John Terry has played in the three prior FA Cup rounds, but the defender's place against United is not guaranteed. And with Chelsea next in action at Stoke five days later, Conte could field his first-choice line-up.
Aside from United's striker crisis, Luke Shaw is back in contention for Monday's clash.
Eric Bailly could also feature after serving a European suspension in Russia, where United emerged unscathed despite concerns over the pitch. Bastian Schweinsteiger remains a doubt with an unspecified complaint.
Opta stats
Manchester United have won seven of their last nine FA Cup ties v Chelsea, but have lost the last two (2007 final, R6 in 2013)
Mourinho has won four of his last six games against teams he previously managed (L2) but was beaten 4-0 earlier in the season on his return to Stamford Bridge.
Chelsea are unbeaten in their last 11 meetings with Manchester United in all competitions (W6 D5), last losing to them 3-2 in October 2012.
United have scored just three times in their last nine clashes with Chelsea, and never more than once in any of those games.
Chelsea and Manchester United have met in the sixth round of the FA Cup three times before, with the Blues progressing twice (1949/50 and 2012/13).
Conte reached the Coppa Italia quarter-finals in each of his three seasons at Juventus, but didn't go onto win the tournament (runners-up 2011/12, semi-final 2012/13 and quarter-final 2013/14).
The last time Mourinho reached an FA Cup semi-final was in 2006/07, going onto beat his current club Manchester United in the final.
Paul Merson's prediction
This is Manchester United's big test! This will show us how far they've come since that 4-0 defeat to Chelsea at Stamford Bridge in the Premier league. Since that game United have lost just two games from 30 matches in all competitions but they haven't really beaten anybody.
They will be without Ibrahimovic and he's Man Utd at the moment. He's carried the team. They will also be getting back late from Russia after their Europa League game and they have to deal with the poor pitch out there. I don't see anything but a Chelsea win. I can't see United getting a result at all.
PAUL PREDICTS: 2-0 (13/2 with Sky Bet)
Betting
Chelsea are Sky Bet's 4/5 favourites to reach the semi-finals within 90 minutes as Manchester United are held as 18/5 outsiders, while extra-time is a 5/2 chance.
The Blues were cut from even-money on the back on Zlatan Ibrahimovic's suspension, while Sky Bet go 9/2 on the tie to be settled on penalties with either side to progress in extra-time is a 13/2 chance.
Diego Costa is the 7/2 favourite in the first goalscorer betting while Marcus Rashford is considered United's main threat at 13/2 to net first in Ibrahimovic's absence.