The 22-year-old Wales winger was substituted after 64 minutes of Wednesday's one-sided 3-1 home defeat to rivals Manchester City in the first leg of the Carabao Cup semi-final.
That result undoubtedly has left the Red Devils with a big mountain to climb when the two teams reconvene hostilities at the Etihad Stadium in three weeks.
And United boss Ole Gunnar Solskjaer might have to plot any unlikely comeback without the services of James, who is said to be 'right on the limit' since mid-December.
The former Swansea City starlet has been a virtual ever-present since his £15 million arrival before the start of the season.
Solskjaer had hoped James would be afforded the opportunity to ease his way into life in the top flight, but a crippling injury list has already resulted in him playing 31 games for club and country so far.