The pair returned to training last week following injury layoffs and will both make their first appearance of the season this evening.
United boss Mourinho has made six changes in all from last weekend's shock 3-2 loss at Brighton & Hove Albion, with Jesse Lingard and Ander Herrera also coming in, while centre-backs Phil Jones and Chris Smalling have been recalled.
The big news as far as the visitors are concerned is that skipper Hugo Lloris starts, despite being arrested and charged for drink-driving on Friday.
Mauricio Pochettino makes two alterations from the 3-1 win over Fulham nine days ago, bringing in Danny Rose and Mousa Dembele for Ben Davies and Davinson Sanchez, likely meaning a switch in formation to four at the back.
Spurs have lost four consecutive league matches away at United without scoring.
Manchester United: De Gea; Valencia, Jones, Smalling, Shaw; Matic, Fred, Herrera; Pogba, Lingard; Lukaku
Subs: Grant, Lindelof, Young, Fellaini, McTominay, Sanchez, Rashford
Tottenham Hotspur: Lloris; Trippier, Alderweireld, Vertonghen, Rose; Dier, Dembele; Alli, Eriksen, Moura; Kane
Subs: Vorm, Davies, Sanchez, Aurier, Winks, Lamela, Llorente
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