Southampton boss Ralph Hasenhuttl expects Nathan Redmond to be sidelined for up to three weeks but is relieved the winger's ankle injury is not more serious.
Redmond went down unchallenged during the midweek Carabao Cup success at Fulham and was seen leaving Craven Cottage on crutches and wearing a protective boot.
Summer signing Moussa Djenepo, who like Redmond was on the scoresheet in last weekend's 2-0 win at Brighton, will also miss Saturday's Premier League clash with Manchester United after picking up a muscle problem during a costly encounter against the Cottagers.
"In the moment it looks that he seems to be out for two, three weeks, I think," Hasenhuttl said of Redmond.
"It can be longer but with good rehab – the next 10 days he has to wear a shoe that he doesn't move his ankle – and then it can be quicker.
"I think it could be worse, even though we are not happy about having injuries after the last game because besides Nathan, also Moussa is injured, he has a problem with his muscle and he is also out for the weekend."
One-time England international Redmond has been rejuvenated under Hasenhuttl and was Saints' top scorer and player of the year during the 2018-19 season.
Speaking about the 25-year-old's impending absence, the Austrian coach added: "(It is a) massive one for our team, absolutely.
"He can make the difference. Every game he is missing is not good for us, that's for sure."
Southampton's 1-0 win in west London on Tuesday has set up a mouthwatering third-round tie against fierce rivals Portsmouth.
The two clubs have not met since the the 2011-12 campaign when Saints won promotion to the Premier League and Pompey were relegated to League One.
Both encounters that season ended in draws, while Saints have not enjoyed victory over their near neighbours since an FA Cup tie in January 2005.
Although Hasenhuttl is keen to focus on the three top-flight fixtures before the trip to Fratton Park on the week commencing September 23, he is aware of the significance of the fixture to Saints supporters.
"I know the history and I know that it's for our fans the only really south coast derby. I think this game doesn't happen for a long time," he said.
"A good game for celebrating football in this special way. For us, a good chance to come in the next round.
"There's still a few days to go to this game so maybe we should focus first on the other challenges we have.
"I know that it will be interesting."
Southampton welcome Ole Gunnar Solskjaer's Manchester United to St Mary's for a lunchtime kick-off on Saturday.
United arrive on the south coast following a surprise 2-1 home defeat to Crystal Palace and a 1-1 draw at Wolves, having missed penalties in both games.
Hasenhuttl does not expect the opposition's recent results to dramatically alter the difficulty of the task facing his players.
"I think as Man United they always have pressure whether they win or lose the game before. I expect the best possible team for us," said Hasenhuttl.
"They also had a few injury problems I think but they have so much quality in their squad.
"When they are coming here, we must have a very good performance from our side.
"The last two games can help us to have more confidence going into the game."