The France international sat out United's win over Huddersfield Town in the FA Cup with a mystery illness, with manager Jose Mourinho seemingly unconcerned over his absence .
And while he has apparently made a full recovery from the complaint, he will be left on the bench come kick-off at the Sanchez Pizjuan.
McTominay, 21, continues in the first team after making a positive impression in United's 2-0 victory at the weekend.
Romelu Lukaku, meanwhile, leads the line alongside Alexis Sanchez, with the front trio completed by Juan Mata rather than Anthony Martial.
Pogba is reportedly unsettled at Old Trafford after being shifted to a more defensive role following the arrival of Alexis, and has been far from his best in recent weeks, with Mourinho leaving him on the bench for the recent league win over Huddersfield.
That dip in form has in turn led to reports he has fallen out with Mourinho, and could leave the club for a second time this summer.
Sevilla: Rico, Navas, Lenglet, Mercado, Escudero, N'Zonzi, Vazquez, Sarabia, Banega, Correa, Muriel.
Substitutes: Soria, Carico, Ben Yedder, Pizarro, Nolito, Roque Mesa, Sandro.
Manchester United: De Gea; Valencia, Smalling, Lindelof, Young; Matic, Herrera, McTominay; Alexis, Lukaku, Mata.
Substitutes: Romero, Bailly, Darmian, Pogba, Lingard, Martial, Rashford.