The Selhurst Park outfit have not beaten United in the league since 1991, losing nine and drawing two of the 11 fixtures to take place during that period.
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But Palace boss Tony Pulis, who himself has never picked up a win over United in the Premier League as a manager, may view this as the ideal opportunity to play the reigning champions, who will be short on confidence having gone three matches without a win.
Pulis' charges have won three of their last four games in the Premier League - a run that has seen them climb to 15th in the table - but with just two points separating Palace from the relegation zone, an unexpected three points would be more then welcome.
United drew 0-0 at Arsenal last time out and face a Champions League last-16 clash against Olympiakos three days after this Saturday's encounter, but Pulis fully expects David Moyes to have his side at full strength at the weekend.
"[Moyes] is a winner," he said. "He wants to win football matches, so he'll pick a team to win at Crystal Palace."
That said, Moyes has become a fan of rotation this term, having not named the same starting XI for any two competitive games.
No Palace player has provided more than one assist in the Premier League this season, but United have their own attacking concerns, with Wayne Rooney having failed to score or assist in his last five matches - his longest such run since 2011.
In recent times, there has not been much to choose between the sides. Since Pulis took charge of Palace at the end of November, Palace have achieved just two points fewer than United, having played one game less.
However, the Welshman insists he is taking a game-by-game approach at Selhurst Park.
"I don't think you can look any further than the next game in this league," he continued. "If you win games you've got to keep your feet on the ground and keep pushing forward.
"If you lose games, you've got to dust yourself down, get up and get ready for the next one. That's the way it's going to be from now until the end of the season."
Palace could be without Jerome Thomas, who has picked up a back problem, while Glenn Murray could be in line for a first start since returning from injury.
Marouane Fellaini, meanwhile, could feature for United for the first time since December 4, while Jonny Evans (calf) remains doubtful.