Having picked up a first ever point at the Emirates Stadium last weekend, Palace will be aiming to repeat the feat at Old Trafford tonight having lost all six of their previous games at the venue.
The Red Devils are currently four points behind Arsenal in the race for the final Champions League spot, and will be hoping to crank up the pressure on the Gunners in the final few weeks of the season.
Palace though come into this game on the back of a four-game unbeaten run, although United have won their last five matches on their own turf.
With both teams in action in the FA Cup semi-finals on the weekend, both Alan Pardew and Louis van Gaal are expected to make plenty of changes to their line-ups as they hope to face each other in the final next month.
Louis van Gaal: "This game against Crystal Palace is very important. We have to win, we need to win, otherwise we cannot close the gap. It is too important to rotate for freshness for the semi-final.
"I don't think there is a lot of distance between Tottenham and Manchester United, but the distance is in points.
"They have won more, they are scoring more and that's because they have more creative players. In my opinion I don't have a senior creative player but I have said that in advance and everybody knows that."
Manchester United: Despite saying that he won't be making too many changes, van Gaal could recall Anthony Martial and Jesse Lingard who sat out United's 1-0 win against Aston Villa on Saturday.
Bastian Schweinsteiger is set to miss the rest of the season with a knee injury, while Ander Herrera is also a doubt with a knock.
Leg-break injury victim Luke Shaw is back in training but won't be considered for this game.
Crystal Palace: Pardew has confirmed that Scott Dann, Joel Ward, Yannick Bolasie and Joe Ledley will all miss the game with minor knocks that shouldn't keep them out of the FA Cup semi-final against Watford.
James McArthur could be included after his recovery from ankle ligament damage, but Dwight Gayle and Marouane Chamakh remain out.
HEAD TO HEAD
|Man United wins||Draws||Palace wins|
Manchester United have never lost to Palace in the Premier League (W10 D3).
The Eagles have failed to score in 10 of their 13 Premier League games against Manchester United and five of six at Old Trafford.
Palace have kept only one clean sheet away to Manchester United in league competition in 18 attempts - October 1970 (1-0).
Marcus Rashford has scored seven goals in his 12 appearances for Manchester United so far, despite attempting only 10 shots on target.
Wayne Rooney has scored 99 Premier League goals at Old Trafford - the only player to have scored 100+ at a single Premier League ground is Thierry Henry at Highbury (114).
Palace are winless in their last eight Premier League away matches (W0 D5 L3) since their last win on the road back on 19th December 2015 at Stoke City.
All three of Emmanuel Adebayor's Premier League goals against Manchester United have been scored at Old Trafford.
Lee Mason is the man in the middle for this game - he has overseen two Palace games this term which were the 2-1 loss to Arsenal in August and the 2-1 win at Southampton in the FA Cup.
Referee: L Mason
Assistants: M Salisbury and S Long
Fourth Official: M Jones
LAST MEETING AT OLD TRAFFORD
8th November 2014
Manchester United 1-0 Crystal Palace
Manchester United moved up to sixth in the Premier League as Juan Mata's second-half goal secured victory over stubborn Crystal Palace.
There was little between the two in the first half, with Fraizer Campbell lobbing over for Palace and Luke Shaw denied for the hosts.
United boss Louis van Gaal brought on Mata after the hour and he made a swift impact, driving in from 20 yards.
Mata hit the post later but his earlier goal proved enough to take victory.
Tickets for away fans will still be available to purchase for season ticket holders and members from the ground before kick-off.
Adults 21-64 £46.00
65+ and 18-20 years £36.50
16-17 years £27
Under 16 £18
For directions on how to get to Old Trafford, read our away travel guide here
Live commentary of all 90 minutes from Old Trafford will be available on Palace Player. Click HERE to log in or sign up.
There will also be constant updates throughout the day at @CPFC