The pair are suspended for one Premier League match game after accumulating their fifth bookings in the competition this term during the recent defeat to Wolverhampton Wanderers at Old Trafford.
Alex Telles is likely to be a leading contender to come in at left-back and McTominay, who scored the winner in the Emirates FA Cup third-round win over the Villans last time out, will need replacing in the heart of the midfield, with a few options available to interim boss Ralf Rangnick.
Victor Lindelof returned after a COVID-enforced absence for the cup victory, while Harry Maguire and Phil Jones will hopefully be fit again for the weekend.