The two England internationals limped out of Saturday's Premier League encounter with Aston Villa and were big doubts for the visit of Villarreal in Wednesday's Champions League tie.
Club captain Maguire is definitely unavailable, as is suspended right-back Aaron Wan-Bisska, but there is a chance Shaw could make the substitutes' bench.
Marcus Rashford and Amad are still working their way back to fitness.
"That's football for you and why we have a big and strong squad," said the manager when asked about the pair by club media's Mark Sullivan.
"It looks like Harry is definitely out.