David de Gea picked up an apparent ankle injury during the warm-up for Manchester United's Europa League clash with Midtjylland on Thursday.
The Spain international began limping United went through their final routines ahead of the last-32 first leg and was withdrawn from the starting line-up. Sergio Romero was named as his replacement.
The news comes just 24 hours after manager Louis van Gaal confirmed that captain Wayne Rooney has joined United's lengthy injury list after picking up a knee ligament problem.
Van Gaal lamented in the build-up to the game that 13 first-team players were unavailable to him through injuries, but any lengthy absence for De Gea - United's Player of the Year in each of the last two seasons - could hit the Dutchman hardest of all.