Former Tottenham forward Erik Lamela leads the line for Sevilla, whose attacking line-up includes a 35-year-old Ivan Rakitic.
On-loan Manchester United defender Alex Telles is on the bench against his parent club and there are two other names familiar to Premier League viewers among the substitutes in Jesus Navas, now 37, and Spurs loanee Bryan Gil.
As expected, Casemiro is back in the Manchester United starting line-up following his four-game domestic suspension. He will partner Marcel Sabitzer in midfield, with the returning Christian Eriksen only on the bench.
Up front, Anthony Martial makes his first start since January having coming off the bench and scored in Saturday’s 2-0 win over Everton. He is flanked by Jadon Sancho and Antony, with Marcus Rashford absent due to injury.
In defence, Harry Maguire drops out for Raphael Varane, the Frenchman partnering Lisandro Martinez at centre-back.
Sevilla team news
Sevilla team to face Man Utd: Bounou, Montiel, Nianzou, Marcao, Acuna, Fernando, Gudelj, Ocampos, Rakitic, Torres, Lamela.
Subs: Dmitrovic, Flores, Telles, Rekik, Suso, Rafa Mir, En-Nesyri, Jesus Navas, Gomez, Gil, Bade.
Man Utd team news
Man Utd team to face Sevilla: De Gea, Wan-Bissaka, Varane, Martinez, Malacia, Casemiro, Sabitzer, Fernandes, Antony, Sancho, Martial.
Subs: Butland, Vitek, Lindelof, Maguire, Eriksen, Fred, Dalot, Weghorst, Pellistri, Elanga, Iqbal.
