Regardless of the results which precede it, United will be desperate to pick up three points in order to keep some distance between themselves and the other Champions League challengers.
Having come from behind to beat Chelsea last Sunday, United will be hopeful of taking that form into their trip to Selhurst Park. With huge games to follow against Liverpool, Sevilla and Brighton in three different competitions, Mourinho will want his troops to be firing for the month ahead.
United will be missing six first-team players for Monday night's fixture. Ander Herrera's muscle injury means he sits out, while Daley Blind remains unavailable as he continues his rehab from an ankle problem.
Marcos Rojo and Phil Jones have also been ruled out with knocks, with Mourinho confirming on Friday that they cannot be considered for selection.
Marouane Fellaini is another player who is out, but he could be back by the end of the month after surgery on a left knee issue. As Mourinho explained on Friday: "He's still a young player, his injury had a little surgery, a minor surgery, and he will be back to play again in a couple of weeks."
Zlatan Ibrahimovic is back in training but is still concerned about the continuing effects of surgery on his ACL damage, meaning he will not be making the trip to south-east London on Monday.
United have no suspension issues, and the same is true of Roy Hodgson's side.
Man Utd potential starting line-up
Jose Mourinho could well stick with largely the same side which beat Chelsea last week, although that's not to say he won't have a number of selection headaches to overcome first.
Eric Bailly is back fit and available, and it may well suit his manager to give him a run-out at Selhurst Park on Monday before the more high-profile fixtures which come later in the month. Either one of Chris Smalling and Victor Lindelof could step aside for the Ivorian should Mourinho decide to bring him into the starting XI.
Jesse Lingard is pushing for a start having headed home the winner against Chelsea, but none of Alexis Sanchez, Anthony Martial and Romelu Lukaku could be claimed to have disappointed at Old Trafford either. Juan Mata could also be considered.
Crystal Palace team news
When United met Palace last, Roy Hodgson's side remained goalless after seven straight defeats to start the season and were facing up to hosting Chelsea next. But having seen off the Premier League champions, the Eagles have been on a remarkable rise which at one point had seen them reach mid-table.
But a backward step of late has seen them slip to 17th on the back of five straight games without a win, and with a continuing lengthy injury list to cope with Hodgson is ever more reliant on a handful of players pulling them out of releagtion trouble.
They could do with more goals out of Christian Benteke and Wilfried Zaha over the remainder of the campaign, with the front pair having grabbed a total of six league strikes between them all season compared to midfielder Luca Milivojevic's seven.
Beyond their extensive injury list, Palace are also without Tim Fosu-Mensah on Monday due to Premier League rules which prevent loanees from taking part against their parent clubs.
TV channel & kick-off time
The match at Old Trafford kicks off at 20:00 GMT on Monday, with live coverage available in the UK on Sky Sports Premier League beginning at 19:00.
Best Opta match facts
Crystal Palace haven’t won any of their 17 Premier League meetings with Manchester United – the most a team has played another without a single victory in the competition (D3 L14).
Indeed, Manchester United are unbeaten in 19 top-flight games against Crystal Palace (W16 D3 L0), since a 0-3 loss at Selhurst Park in May 1991 courtesy of goals from Ian Wright and John Salako (2).
Crystal Palace have only scored in four of their 17 Premier League games against Man Utd, netting just five goals in total.
Crystal Palace have lost all eight of their Premier League games this season that have not featured Wilfried Zaha, scoring just once and conceding 18 in these games.
Manchester United haven’t lost three consecutive Premier League away games since January 1996, while Jose Mourinho has only lost three straight away league games once in his managerial career (August 2006 with Chelsea).
Anthony Martial and Romelu Lukaku have combined for six Premier League goals this season (3 assists each to each other) – no Man Utd partnership has had more in a single Premier League campaign, with Martial/Rooney in 2015-16 the last duo to get this many.
Paul Pogba has scored in both of his Premier League games against Crystal Palace – they’re currently the only team he’s scored both home and away against in the competition.
Anthony Martial has had a hand in more goals as a substitute than any other player in the Premier League this season (6, 4 goals 2 assists).