Scott McTominay has been a fixture in Solskjaer's sides for big games throughout the campaign, and with the likes of Leicester City and Liverpool scheduled to visit Old Trafford next week, he could be rested in Rome. Veteran midfielder Nemanja Matic could be brought into the side instead of the Scot to anchor their midfield.
Matic looked in great touch during his previous start against Granada in England, and he could be expected to start alongside Fred in the middle of the park.
The two holding midfielders are most likely to line up behind Manchester United's star man Bruno Fernandes in the attacking midfield role. Fernandes was in surreal form during the first leg as he scored two goals and set up two more, and is in line for another start.
Solskjaer could potentially offer Donny van de Beek some valuable minutes over the course of the game, but the Dutchman is unlikely to start ahead of Fernandes.
Solskjaer dropped a hint over his team selection by dropping Edinson Cavani for the canceled game against Liverpool, and could do so once again in Rome. The Uruguayan's absence could pave the way for Mason Greenwood to start the game and make his 100th appearance for Manchester United, becoming only the fifth player to hit this landmark for the side as a teenager.
Marcus Rashford could reprise his role on the left-hand side of the attack, with Paul Pogba dropping to the bench. Rashford hasn't been nearly as effective from the right as he was on the left for a large part of the campaign, and the English superstar could play off the left.
Welsh winger Daniel James could complete the front three by coming in on the right-hand side of the attack in Rome. James has already started away at Milan, Real Sociedad, and Granada, and could be in line for his sixth start of the Europa League campaign against AS Roma.
The likes of Amad Diallo and Shola Shoretire could potentially come on for some minutes as the game goes on as well.
Predicted XI: David de Gea; Aaron Wan-Bissaka, Eric Bailly, Harry Maguire, Alex Telles; Fred, Nemanja Matic; Daniel James, Bruno Fernandes, Marcus Rashford; Mason Greenwood.