Manchester United youngsters Ethan Laird, Di'Shon Bernard and Dylan Levitt will make their debuts against Astana in the Europa League.
With progress to the round of 32 already secured, Ole Gunnar Solskjaer has brought a largely inexperienced squad to Kazakhstan.
First-team regulars Luke Shaw, Jesse Lingard and Axel Tuanzebe are set to start at the Astana Arena, where 36-year-old Lee Grant will make his full debut.
But the rest of the group are young academy products, 10 of whom have yet to make their senior debut.
"Common sense," Solskjaer said of the reasoning behind his selection of such a young panel.
"We have done great to qualify after four games, so it gives us an opportunity to give game time to the experienced lads who need it: Axel, Luke and Jesse.
"They've not really had too many games and they're coming back from injuries.
"It's a great chance for me to give Lee his first start for the club.
"It's hard with the young kids to give them enough games against men, professional games.
"We've got the EFL Trophy and for me this is a great chance for me to see them all together."
Another of the young players yet to make his debut is Max Taylor, who has been named in the senior squad for the first time at the end of a year that started with chemotherapy having been diagnosed with testicular cancer.
"It's a fantastic story, to see him coming back," Solskjaer said of the 19-year-old defender.
"I met Max very early after I got the job and to have seen his journey back to full fitness and the way he's conducted himself, and it's something he'll always have with him. He's been through something no one should have to go through but he's come through the other end.
"He's an inspiration for all the players.
"You can see when he's out on the pitch there's no fear anymore, he's had fear in his life, when you're on the football pitch you should enjoy yourself and I hope we can see him progress in his career.
"It's a chance for us to give him extra motivation as well."