There's no such thing as a 'gimme' in the Premier League but this looks as close to one as it's possible to have - it would be a major surprise if United come away with anything other than three points.
United have been in devastating mood so far this season having amassed 29 goals in ten outings so far, and a win here would - temporarily at least - send the side three points clear at the top.
City travel to Chelsea in the late game, so with one or both to drop points there is an added incentive for Jose and the team to take control of the Premier League summit.
The struggling Eagles have endured a woeful start to the season and made unwanted history in their 5-0 defeat across town at the Etihad last time out.
That result meant that Palace became the first team in English football history to lose their opening six matches without scoring a goal.
Frank de Boer was sacked after their 1-0 loss at Burnley and he was replaced by much-travelled manager Roy Hodgson, who has been unable to reverse their fortunes so far.
Michael Carrick and Phil Jones missed the trip to Moscow with injury, and the duo remain sidelined for the visit of Palace.
Paul Pogba is still out with a long term hamstring problem, and Marouane Fellaini is doubtful but Antonio Valencia is set to return.
Anthony Martial was taken off in Moscow with a slight thigh problem and will be assessed.
For the visitors, Christian Benteke has been ruled out for six to eight weeks having picked up a knee ligament injury.
Ex-Red Wilf Zaha, James Tomkins and Ruben Loftus - Cheek are also ruled out, and United loanee Tim Fosu - Mensah is ineligible.
United boss Jose Mourinho refused to take Palace for granted and has called on his side to show a strong mentality.
He said: "We played Wednesday night and arrived back in Manchester at 4am Thursday and now we have to play Saturday so our mentality and attitude is very important.
"Roy is an experienced manager, he has good players and Palace are a good club, they have a long time to fight to reach their objectives.
"Pogba is a long term injury, the same as Rojo and Ibrahimovic, I cannot have hope like with Valencia and Jones who I can see in training and have a positive answer.
"My focus is on the players I have and this game against Palace so I don't speak about the injuries."
Form guide: United D W W W W W Crystal Palace W L L L W L
Match odds: United 1/6 Draw 6/1 Crystal Palace 14/2
Referee: Mike Dean