Jadon Sancho and Wout Weghorst will join Marcus Rashford in Manchester United's front three against Barcelona in the Europa League on Thursday night.
The 20-time English champions are at Camp Nou for the first leg of their knockout round playoff in the competition.
Lisandro Martinez and Marcel Sabitzer are both suspended for the Red Devils, while Donny van de Beek, Christian Eriksen, Antony, Scott McTominay and Anthony Martial are on the injured list.
There had been suggestions that Man United head coach Erik ten Hag could switch to a back five for this match, with Victor Lindelof and Harry Maguire pushing to start.
However, Luke Shaw will play alongside Raphael Varane in the middle of the defence, with Aaron Wan-Bissaka and Tyrell Malacia playing in the full-back positions.
In midfield, there is a return for Casemiro, who is currently suspended in the Premier League.
Meanwhile, Fred and Bruno Fernandes are also in the starting XI for the visitors to Camp Nou.
Further forward, Rashford was a guaranteed starter, and he will be joined by Sancho and Weghorst.
Sancho has recently returned to the first team following a spell out, while Weghorst has been a key player for the club since his arrival on loan from Burnley in January, but the Netherlands international has only found the back of the net on one occasion for Ten Hag's side.
Diogo Dalot, Lindelof, Maguire, Facundo Pellistri and Alejandro Garnacho are among the substitutes for the visitors.
MANCHESTER UNITED: De Gea; Wan-Bissaka, Varane, Shaw, Malacia; Fernandes, Casemiro, Fred; Sancho, Weghorst, Rashford
Subs: Butland, Heaton, Dalot, Lindelof, Maguire, Mainoo, Pellistri, Iqbal, Elanga, Garnacho
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