David de Gea was replaced by Dean Henderson at half-time during Manchester United's Premier League clash with Southampton.
De Gea's knee appeared to collide with the post as he scrambled to try and save James Ward-Prowse's pinpoint free kick to no avail.
Ward-Prowse's goal put the Saints 2-0 up at St Mary's after Jan Bednarek opened the scoring with a glancing header.
De Gea was able to finish the remaining 12 minutes of the half but Ole Gunnar Solskjaer was forced into the substitution at half-time.
The United boss faces a nervous wait for news on severity of the injury sustained by his No.1.
De Gea has started all nine of the Red Devils' Premier League games this season and all but one of their Champions League group-stage fixtures.
Meanwhile, Henderson came on for his fourth appearance for United and his first for the club in the Premier League.
The 23-year-old - who penned a lucrative new deal last summer - has seen limited action this season but Solskjaer insists he is content with his back-up status at Old Trafford.
"He has come back in, he is training really well, he is maturing," Solskjaer said last week "He is training with, for me, one of the best goalkeepers in the world. He has got potential to be one of the best goalkeepers in the world.
"It's a great competition between them [Henderson and De Gea], so I don't buy that argument that it is a make or break for him."
The Norwegian added: "Dean wants to stay at Manchester United and play for Manchester United."
Against Southampton, Solskjaer also made another half-time change as Edinson Cavani came on for Mason Greenwood in a shake-up of the forward line.
Cavani took just 14 minutes to make an impact on the match, assisting Bruno Fernandes as United halved the deficit.
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