Jose Mourinho has dropped Zlatan Ibrahimovic to the bench for Chelsea's visit to Old Trafford, with Marcus Rashford instead leading the line.
Henrikh Mkhitaryan has also been given time to convalesce following Man Utd's Europe League exertions on Thursday.
With Anthony Martial out of the matchday 18 entirely there is a first ever captaincy for Ashley Young, who is likely to start on the left of a five-man midfield in his 160th appearance for the club. Jesse Lingard is likely to provide a central attacking foil just behind Rashford in a 3-5-1-1 formation similar to the one Mourinho employed in the 1-0 FA Cup defeat to the Blues at Stamford Bridge in March.
Elsewhere, David de Gea returns in goal after injury, with Sergio Romero returning to the bench.
Meanwhile, the big news for the away side is that Thibaut Courtois hasn't made the squad due to suffering an ankle injury in training.
Otherwise, Chelsea are largely unchanged from the 3-4-3 side which has served Antonio Conte so well since earlier this season.
A victory for the visitors would see them regain a seven-point advantage at the top of the Premier League table after Tottenham's comfortable 4-0 victory over Bournemouth on Saturday.
Man Utd XI: De Gea; Darmian, Bailly, Rojo; Valencia, Fellaini, Herrera, Pogba, Young; Lingard; Rashford.
Subs: Romero, Ibrahimovic, Carrick, Blind, Mkhitaryan, Shaw, Fosu-Mensah
Chelsea XI: Begovic; Azpilicueta, David Luiz, Cahill; Moses, Kante, Matic, Alonso; Pedro, Diego Costa, Hazard.
Subs: Eduardo, Zouma, Terry, Loftus-Cheek, Fabregas, Willian, Batshuayi.