Roma rely on Edin Dzeko, Henrikh Mkhitaryan and Chris Smalling against Manchester United’s Edinson Cavani, Paul Pogba and Bruno Fernandes in the Europa League semi-final.
The first leg kicks off at Old Trafford on Thursday at 20.00 UK time (19.00 GMT).
This is the biggest game of the season for the Giallorossi, who have slipped down the Serie A standings to seventh place and risk not qualifying for Europe at all next term.
The injury crisis is finally calming down a little, although Pedro Rodriguez, Riccardo Calafiori, Nicolò Zaniolo and Stephan El Shaarawy are still out of action.
Gianluca Mancini sits out a ban, so Chris Smalling is back in the starting XI following his long injury lay-off and faces his former club.
So does Mkhitaryan, with Lorenzo Pellegrini and ex-Manchester City striker Dzeko chosen ahead of Borja Mayoral.
Jordan Veretout is an important comeback too, with Amadou Diawara preferred to Gonzalo Villar, and Leonardo Spinazzola gets his first start since picking up an injury against Ajax.
Manchester United have almost a full squad to choose from and go into this tie as the undoubted favourites, having dropped down from the Champions League.
Only Anthony Martial and Phil Jones are on the treatment table, as Marcus Rashford has recovered from an ankle issue to start.
There are quite a few ex-Serie A stars in Ole Gunnar Solskjaer’s side, including Paul Pogba, Edinson Cavani and Bruno Fernandes.
Harry Maguire, Luke Shaw and Scott McTominay return after they were suspended for the second leg of the quarter-final with Granada.
Roma beat Manchester United only once, 2-1 in the first leg of the 2007 Champions League quarter-final, famously crumbling 7-1 in the second match.
Other than that opening clash, the Giallorossi managed one draw and four defeats.
They most recently crossed paths in the 2007-08 Champions League quarter-final, losing 2-0 at home and 1-0 away.
Manchester United: De Gea; Wan-Bissaka, Lindelof, Maguire, Shaw; McTominay, Fred; Rashford, Fernandes, Pogba; Cavani
Man Utd bench: Grant, Henderson, B Williams, Van de Beek, Mata, James, Bailly, Greenwood, Diallo, Alex Telles, Matic, Tuanzebe
Roma: Pau Lopez; Smalling, Cristante, Ibanez; Karsdorp, Diawara, Veretout, Spinazzola; Pellegrini, Mkhitaryan; Dzeko
Roma bench: Mirante, Fuzato, Kumbulla, Santon, Peres, Villar, Ciervo, Darboe, Perez, Mayoral
Ref: Del Cerro Grande (ESP)