The Red Devils need to beat the Eagles to be sure of sixth spot in the table, which would see them qualify for next season's Europa League ahead of West Ham United.
However, Ralf Rangnick's side will allegedly be without the services of their leading goalscorer, with Ronaldo set to miss the contest at Selhurst Park.
Ronaldo missed out against Aston Villa and Manchester City earlier this season with a similar problem, and he is now expected to be sidelined for his side's last match of the 2021-22 campaign.
The Portugal international has enjoyed an impressive return to Old Trafford, finding the back of the net on 24 occasions in 38 appearances in all competitions, in addition to contributing three assists.
Ronaldo has 18 Premier League goals, while he scored six times in seven Champions League appearances, as Rangnick's team were eliminated by Atletico Madrid in the last 16.
There has been a host of speculation surrounding the forward's future in recent weeks, with claims that he could leave Man United this summer, one year before the end of his contract.
However, Ronaldo is set to stay at Old Trafford to work under incoming head coach Erik ten Hag, who has revealed that he is looking forward to managing the former Sporting Lisbon youngster.
"He is a true winner and a magnificent player. I can't wait to work with him," Ten Hag said in his final interview with Ajax.
Meanwhile, Ronaldo hailed the incoming manager in a recent interview with Man United's official website, seemingly confirming that he will stay at the club despite their lack of Champions League football next term.
"I know that he has done a fantastic job at Ajax, and that he is an experienced coach, but we have to give him time," said Ronaldo. "Things must change the way he wants.
"If he does well, all of Manchester United will be successful, so I wish him well. We are all happy and excited [about his arrival], not only as players, but as fans as well. We have to believe that next year we can win titles."
Ronaldo has now scored 142 goals and registered 71 assists in 330 appearances for Man United during his two spells with the club.
Man United are currently two points clear of seventh-placed West Ham in the table, with the Hammers finishing their campaign away to Brighton & Hove Albion. body check tags ::