Wayne Rooney is one of a number of familiar faces to return to Old Trafford in a match between two sides who have started the season in starkly contrasting form.
United have set the early Premier League pace with ten points from a possible 12, whilst Everton - despite a near £200 million summer spending spree - have suffered three straight defeats and are 16th in the table.
Their latest loss came in the Europa League on Thursday when Ronald Koeman's team produced a sluggish, abject performance in a 3-0 reverse away to Atalanta.
Despite the talented and expensive squad at his disposal, they are yet to gel and Koeman has been unable to reproduce last season's form that saw a seventh-placed finish and that European spot.
Rooney faces his old side for the first time since his return to Goodison Park on a free transfer, with Morgan Schneiderlin and Michael Keane also set to face their former Old Trafford employers.
For United, in-form duo Romelu Lukaku will come up against his old team for the first time since his £75m move in the summer, with ex-Toffee Marouane Fellaini also set to feature.
Paul Pogba is out for a "few matches" with the hamstring injury he picked up against Basel, but Phil Jones and Eric Bailly will be available having served European bans.
Luke Shaw and Marcos Rojo have both stepped up their recovery but this one will come to soon for both.
Ross Barkley and James McCarthy miss out for the visitors, with long-term absentees Ramiro Funes Mori, Seamus Coleman and Yannick Bolasie all sidelined.
United boss Jose Mourinho expects a difficult match for the team against a strong Everton side, despite the Toffees recent struggles.
He said: "I'm not going to analyse their form, I'm just going to say that they are a dangerous opponent with incredible investment.
"Investment of the teams that want to play for the title, so I think that this is their objective, or maybe the top four.
"They have lots of quality players, a good team with a good manager so it is a very difficult match for us.
"Wayne (Rooney) is clearly one of the most important players in the history of Manchester United, so I hope our fans will show him the respect he deserves before and after the match."
Form guide: United L W W W D W Everton W D D L L L
Match odds: United 1/3 Draw 4/1 Everton 9/1
Referee: Andre Marriner