Willy Kambwala did not travel down to London alongside his teammates on Saturday due to an injury, and with Raphael Varane, Lisandro Martinez, Victor Lindelof and Jonny Evans also out, Casemiro will start in the middle of the defence alongside Harry Maguire.
There is just one change from the side that started against Bournemouth in the Premier League last weekend, with fit-again Scott McTominay coming in for Kambwala.
Antony is also back in the squad after missing the clash with Bournemouth.
Youngsters Louis Jackson, Harry Amass, Habeeb Ogunneye and Ethan Wheatley are all on the bench for the 20-time English champions due to the team's injury issues.
As for Coventry, there is a spot in the XI for Callum O'Hare, who was a second-half substitute in the 3-0 defeat to Birmingham City in the Championship last time out.
Ellis Simms is the team's leading goalscorer this season with 18 goals in all competitions, while Haji Wright has netted 17 goals during a strong campaign for the club.
Coventry City: Collins; Latibeaudiere, Thomas, Kitching, Bidwell; Eccles, Sheaf; Van Ewijk, O'Hare, Wright; Simms
Subs: Wilson, Binks, Dasilva, Kelly, Allen, Godden, Torp, Tavares, Andrews
Manchester United: Onana; Dalot, Maguire, Casemiro, Wan-Bissaka; McTominay, Mainoo; Garnacho, Fernandes, Rashford; Hojlund
Subs: Bayindir, Eriksen, Amad, Antony, Forson, Amass, Ogunneye, Jackson, Wheatley