Southampton will be without key players Nathan Redmond, Moussa Djenepo and Michael Obafemi after the trio suffered injuries in their 1-0 League Cup win over Fulham, manager Ralph Hasenhuettl said.
Redmond appeared to fall awkwardly on his ankle during the second half at Craven Cottage on Tuesday and needed to be helped off the pitch by medical staff.
Hasenhuettl confirmed Redmond, who played every league game last season and was involved in 10 goals, would be sidelined for at least a couple of weeks.
"At the moment it looks like (Redmond) will be out for two-three weeks," Hasenhuettl told reporters ahead of Saturday's Premier League match against Manchester United.
"He could be out longer and he has to wear a protective boot for the next 10 days but it (his recovery) could be quicker. It could also have been worse, we're not happy about having injuries after the last game.
"He will be a massive loss for our team for sure. He can make a difference and I'm happy that it's not worse because it could've been and then the impact would have been worse for us. Every game he is missing isn't good for us."
Ireland international Obafemi, who scored the winner at Fulham, will also not play a part after he too came off with cramps. Close season recruit Djenepo is out with a muscle injury.
"Michael Obafemi cramped a little bit and maybe the game at the weekend is too much for him after the game on Tuesday," Hasenhuettl added.
"Moussa is also injured. He has a problem with his muscle and is out for the weekend."