Eric Bailly returned to Manchester United training on Tuesday but Anthony Martial, Luke Shaw and Chris Smalling were all absent.
Bailly played his first match for two months in last week’s draw with Arsenal but then sat out Saturday’s victory over Fulham, which Martial and Shaw also missed.
Smalling started that game but was replaced in the second half after suffering an injury.
With qualification for the Champions League knockout stages already secured ahead of Wednesday’s trip to Valencia, Jose Mourinho will not take any risks and is likely to rest a number of players.
He has already announced that Paul Pogba, who has been left out of the starting line-up for the last two games, and Andreas Pereira will start, and goalkeeper Sergio Romero is also set to play.
Diogo Dalot, who has shone on his first two Premier League starts, looks likely to be rested after missing training along with fellow defender Matteo Darmian, while Victor Lindelof and Alexis Sanchez are definitely sidelined through injury.
There could be spaces on the plane, meanwhile, for 17-year-old academy stars Mason Greenwood and James Garner, who both took part in the session at Carrington.
United fans will no doubt be excited to see from fresh faces in the squad, especially after what has been frustrating first half of the season.
Pereira will be against the side he played for on loan last year and has become somewhat of a fan favourite due to his undeniable ability despite the lack of game time.