"He's just never really recovered from the knocks he had, he was away with Holland a week or so ago and he's got two bad toes and he's been complaining about his groin a little bit," United manager David Moyes told Sky Sports.
"So we took the chance to see if we could rest him tonight and get him ready for the weekend (when United host Stoke City in the Premier League)."
The Dutchman's absence means a start for Mexico striker Javier Hernandez in the Group A match.
(Reporting by Sonia Oxley; Editing by Stephen Wood)
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