David Moyes' side need a point to secure top spot in Group A and avoid most of Europe's heavyweights in the last 16, but the Scot is also hopeful of a morale-boosting performance at Old Trafford after successive home Premier League defeats.
With Michael Carrick also ruled out by an Achilles injury and Darren Fletcher not registered for European competition, Moyes will be counting the bodies ahead of Tuesday's clash.
Speaking after Saturday's 1-0 defeat to Newcastle, Moyes said his side needed to find ways to win games when they weren't playing well.
"We've got roughly the same squad that was champions last year," he said. "We've not changed an awful lot in that period.
"I need to make sure I'm getting the best out of the players and we are performing as well as we possibly can.
"I do think we can play better but there were a lot of games last year where Manchester United didn't play particularly well and maybe, in a game like that, sneaked it with a goal."
You can watch Moyes' news conference ahead of the Shakhtar Donetsk game live on Sky Sports News from 2pm.