United won the first leg of their quarter-final tie 2-0 in Spain last week, meaning Granada must score at least twice at Old Trafford to stand any chance of reaching the last four of the competition.
The Red Devils' dominant position would suggest Ole Gunnar Solskjaer may take the chance to rest some players, but the last-32 would suggest otherwise.
With United 4-0 up against Real Sociedad in the round of 32 heading into the home leg, Solskjaer opted for a strong starting XI with the likes of Bruno Fernandes starting.
Solskjaer is also without three key players - catain Harry Maguire, Luke Shaw and Scott McTominay - who are all suspended following yellow cards in the first leg, while Rashford will not be involved.
Rashford managed 72 minutes of Sunday’s 3-1 Premier League win at Tottenham but was absent from training on the eve of Thursday’s return fixture against Granada. Eric Bailly, Phil Jones and Anthony Martial remain sidelined.
The club said: “Daniel James is fit, despite missing the win at Tottenham through injury, but Marcus Rashford had to sit out training on Wednesday and is, therefore, doubtful for the tie.”
Following Sunday's impressive 3-1 Premier League win at Tottenham, United are in form and on course for a top-four finish - and with a home tie against Burnley on Sunday, Solskjaer can concentrate on warding off a potential fightback by Granada.
Manchester United XI: De Gea; Wan-Bissaka, Lindelog, Tuanzebe, Telles; Matic, Fred; Greenwood, Bruno Fernandes, Pogba; Cavani
Subs: Grant, Henderson, Fish, Williams, Amad, James, Mata, Van de Beek, Elanga, Rashford, Shoretire
Injury list: Martial, Jones, Bailly, Rashford