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
Bayer Leverkusen 
Rot-Weiss Oberhausen 
Hibernian 
Rangers 
VFB Stuttgart 
Ajax 
Eintracht Frankfurt 
FSV Mainz 05 
Werder Bremen 
Twente 
Celtic 
ST Mirren 
Liverpool 
Manchester Utd 
Paris Saint Germain 
Monaco 
Marseille 
Le Havre 
Roma 
Lazio 
Bayern Munich 
Spvgg Greuther Furth 
Fortuna Dusseldorf 
Feyenoord 
Red Bull Salzburg 
Real Madrid 
Inter 
AC Milan 
Sporting CP 
FC Porto 
Arsenal 
Newcastle 
CD Eldense 
Valencia 
Athletic Bilbao 
Barcelona 
Benfica 
SC Braga 
Dundee Utd 
Tottenham 
Mallorca 
Everton 
Peterborough 
Dundee 
Nantes 
Concarneau 
Bordeaux 
Borussia Dortmund 
Como 
Accrington ST