Jose Mourinho's United visit on the back of European commitments while Arsenal boss Arsene Wenger will be hoping for a morale-boosting win over his long-term rival.
Here, Press Association Sport looks at five of the biggest talking points ahead of the game.
WILL JOSE STICK TO HIS WORD?
Mourinho has said he intends to make changes for the game
The Red Devils travel to the Emirates Stadium on the back of a 1-0 win in the opening leg of their Europa League semi-final in Celta Vigo
The return leg against the Spaniards is next Thursday and Mourinho has suggested he will rest key players at Arsenal as he aims to win the Europa League
With Marcus Rashford and Ashley Young both limping out in Vigo, the Portuguese still has several injury worries but can he seriously take Arsenal lightly and risk blowing any chances of reaching the Champions League courtesy of a top-four finish?
WENGER'S TIME TO FINALLY STRIKE
If Mourinho does make wholesale changes, long-term nemesis Arsene Wenger will have no excuse as he chases a first Premier League win over the former Chelsea boss
The under-fire Wenger has failed to record a victory over Mourinho in their previous 12 league encounters but needs the three points this time for much more than personal pride
The Gunners boss remains under pressure following a string of disappointing results and, with his current deal expiring at the end of the season, another protest is planned before the United game by those fans who want to see change.
A SIGN OF THE TIMES
A meeting between Arsenal and United at this stage of the season some 15 years ago would have undoubtedly been a huge clash in the title race
The recent rivalry between the two clubs stems from the years when the pair dominated the Premier League, with their fixtures against one another always the main attraction of the campaign
Now though, they go into Sunday's match down in fifth and sixth, as also-rans in the title run-in and with mainly pride to play for
Wenger said it is proof that other team's have caught up but, in truth, a number have since gone on to surpass the current Arsenal and United sides.
WHICH OZIL WILL SHOW UP?
Mesut Ozil has again seen the finger pointed at him in recent weeks as he seems to drift in and out of games on a routine basis
The German World Cup winner is a clear talent but struggles to take a match by the scruff of the neck
He did, however, star in Arsenal's 3-0 win over United in this fixture last season as he and Alexis Sanchez put the visitors to the sword, scoring all three goals between them in the opening 20 minutes of the game
That is the kind of display Wenger, and the Arsenal fans, will be hoping to see repeated this time out and not the peripheral figure from last Sunday's north London derby defeat to Tottenham, where the only thing Ozil kicked with any note all afternoon was a frustrated boot at a door when told he had to take a drugs test.
UNITED BORE IF THEY CAN AFFORD TO DRAW
Mourinho has taken goalless draws away from both Liverpool and Manchester City this season after fine examples of a rearguard action
A change in personnel may lead to the United boss deploying similar tactics against Arsenal, picking a side of bigger, strong athletes to keep the Gunners at bay
It may not be the free-flowing, attacking football most United fans were brought up on, but it can be effective
But if United are to maintain any sort of push towards a top-four finish, it may be a case of having to try something slightly different and take all three points back up the M6.
Source : PA