Trailing 2-0 from last week's meeting, the Spanish surprise package will be forced to cope without Domingos Duarte and Yan Eteki, both of whom picked up their third cautions of the tournament in the first-leg defeat.
Eteki was never expected to displace Maxime Gonalons or Manchester City loanee Yangel Herrera in the middle of the park, but Duarte's spot in defence should be filled by German Sanchez, unless Martinez takes a punt on the inexperienced Nehuen Perez.
Quini - deputising at left-back - scored an 86th-minute winner for his side against Real Valladolid at the weekend, but with the 31-year-old ineligible for the Europa League, Carlos Neva is in line to start at Old Trafford.
Chelsea loanee Kenedy was not involved at the weekend after sustaining an ankle injury in the first leg, and with his participation here also in serious doubt, Darwin Machis is expected to start on the left-hand side.
The ineligible Fede Vico will be replaced in the middle by Angel Montoro, while Roberto Soldado - back from a domestic suspension - and Luis Suarez - only just back from injury - will battle it out to spearhead the attack.
Granada possible starting lineup:
Silva; Foulquier, Sanchez, Vallejo, Neva; Herrera, Gonalons; Puertas, Montoro, Machis; Suarez