The Red Devils face Wolves hoping to maintain the momentum gained from their 4-0 thrashing of Chelsea on the opening weekend of the new Premier League season.
Wolves beat Manchester United at Molineux twice last season under Ole Gunnar Solskjaer, both in the league and in the FA Cup quarter-finals.
And Solskjaer chose to axe six players from the travelling squad for the trip to Wolverhampton.
None of Chris Smalling, Marcos Rojo, Matteo Darmian, Diogo Dalot, Fred or Alexis Sanchez were spotted getting off the team bus, per the Manchester Evening News.
It marks the second successive match that the sextuplet have missed out on the travelling squad, casting uncertainty over the future of Rojo in particular.
The Argentine defender has been tipped to leave Old Trafford this summer and almost joined Everton on transfer deadline day.
He has been linked with a loan move to Fenerbahce in recent days.
Right-back Dalot will be particularly disappointed after being snubbed for the second consecutive match.
The Portugal international occasionally played in an advanced right midfield role last term but summer signings Aaron Wan-Bissaka and Daniel James mean there is less available game-time for the 20-year-old.
Alexis Sanchez is meanwhile making his way to full fitness after playing in the Copa America for Chile, though Inter Milan are hoping to sign the 30-year-old on a season-long loan.
Solskjaer said of Sanchez recently: “Alexis is such a professional and he comes in working every single day, really hard, and he wants to be part of this.
“It’s these stories again that he’s been put in the reserves and all this – of course he hasn’t.
“He’s part of our squad and he’s a very, very good player. He’s had three weeks now, so he’s a few weeks behind the rest but he’s very close to being part of it.”
And the Norwegian coach is also hopeful midfielder Fred can play his part this year, although he will not be involved at Wolves.
The £50million Brazilian underwhelmed in his first season at the club last term.
But Solskjaer said: “Your team will always play better if settled and have a good foundation and not conceding goals.
“Good teams I played in we always had a strong base, a keeper, settled backline and we hope to provide that for our atttackers and midfielders. ‘We believe Fred is going to have a big season as well.”
Man Utd travelled to Wolves with a 21-man contingent but Angel Gomes, Lee Grant and Phil Jones were all left out of the match-day squad, with Solskjaer only able to name 18 players to be involved.
The manager makes one change to the team that defeated Chelsea, with James coming into the starting line-up after scoring off the bench against the Blues.