The Eagles had fought their way out of the relegation zone after losing their first seven league games of the season, but the Selhurst Park club is back in trouble, with the teams around them rallying.
Date: Monday, March 5
Time: 8 p.m. (GMT); 3 p.m. (ET)
TV: Sky Sports Premier League (UK), NBCSN (U.S.)
The season has not developed how United would have liked it to, with Mourinho's side battling for second place while neighbours Manchester City streak to the title.
United fans have had to swallow their pride as the blue moon has risen over their city while the Red Devils have failed to entertain and endured some difficult performances.
None of this will worry Mourinho, who is typically focused on the bigger picture rather than popularity contests.
United have held the runners-up spot for most of the campaign, but the top sides have merged since the turn of the year. Liverpool and Spurs have crawled their way up the table in recent weeks. The former moved into second place with their win over Newcastle on Saturday, forcing Mourinho to look over his shoulder on the season's homestretch.
Palace staged a recovery after appointing former England boss Roy Hodgson as manager in September, but the south London club has been sucked back into the dogfight at the wrong end of the division.
As West Bromwich Albion struggle to stay afloat in last place, eight points from safety, the Eagles are in a scrap with eight teams that could all fill the remaining two relegation places come the end of the season.
Per Luke Brown of The Independent, Hodgson's early achievements at Selhurst were recognised when he was named manager of the year at the London Football Awards. However, the season could end in disappointment if Palace continue their recent form—they are without a league win since Jan. 13's victory over Burnley.
On Friday, Mourinho revealed his squad has been hit with injuries.
Speaking to MUTV, the United boss said Phil Jones, Marcos Rojo, Daley Blind, Zlatan Ibrahimovic, Marouane Fellaini and Ander Herrera will miss the trip to Selhurst Park.
Mourinho said the following of Fellaini, who has not started a game since United's UEFA Champions League defeat to FC Basel on Nov. 2:
"He's still a young player, his injury had a little surgery, but a minor surgery, and he will be back to play again in a couple of weeks.
"If we proceed in the Champions League beyond Sevilla, I think he will be ready for a hypothetical quarter-final. He will be ready for a hypothetical FA Cup semi-final. He will be ready for the last couple of months of our Premier League fight."
Per Jim Sheridan of The Sun, Palace's Wilfried Zaha is on his way to recovery after a spell out injured but will not be ready to face his former club. However, Jeffrey Schlupp and Martin Kelly could return to duty for the Eagles.
Both United and Palace need to end the season with a touch of class, and the visitors will continue to be scrutinised if they do not succeed on away trips to lesser opponents.
As City get set to be crowned champions of England, the Red Devils must prove they are in a position to compete with their neighbours next term.
Sky Blues coach Pep Guardiola has validated his football philosophy's value at the Etihad Stadium, and Mourinho must replicate this success at the Theatre of Dreams or face a potential exit.
The Portuguese has done just enough to maintain the support of the Stretford End, but it is essential United win games convincingly down the homestretch.