The Dutch custodian has been playing in his side's cup games this term and Mauricio Pochettino has kept faith in the club's second-choice stopper against the Red Devils.
Pochettino has made six changes in total from the XI that drew 1-1 against Brighton & Hove Albion, with Kieran Trippier, Davinson Sanchez, Eric Dier, Mousa Dembele and Dele Alli also drafted back in for Spurs.
United, meanwhile, have made five alterations to his side from Wednesday's 2-0 win at Bournemouth.
Manchester United: De Gea; Valencia, Jones, Smalling, Young; Matic, Herrera, Pogba; Lingard, Lukaku, Sanchez
Subs: Pereira, Darmian, Lindelof, Fellaini, Mata, Martial, Rashford
Tottenham Hotspur: Vorm; Trippier, Sanchez, Vertonghen, Davies; Dier, Dembele; Eriksen, Dele, Son; Kane
Subs: Lloris, Aurier, Alderweireld, Wanyama, Sissoko, Lamela, Lucas
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