Southampton striker Danny Ings will undergo knee surgery on Thursday and could miss up to six weeks, according to manager Ralph Hasenhuttl.
Ings injured his knee in Southampton's 4-3 win at Aston Villa on Sunday and a scan has confirmed the England international requires surgery.
"At the moment it looks like he is out for four to six weeks," said Hasenhuttl, ahead of Friday's match against Newcastle - live on Sky Sports Premier League.
"He'll have a small surgery tomorrow (Thursday) morning. It could be worse, but he'll be out and it's not good news for us."
Ings was forced off in the 85th minute at Villa Park having earlier scored his fifth Premier League goal of the season.
The 28-year-old was injured in a challenge from Villa substitute Trezeguet and had a scan the following day, which Southampton said had provided "favourable" results.
But the former Burnley and Liverpool forward, who has previously suffered two serious knee injuries which led to long spells on the sidelines, will now be absent as Southampton seek to build on a strong start to the season.
The Saints are fifth in the Premier League and play Newcastle, Wolves, Manchester United, Brighton, Sheffield United and Arsenal in the next six weeks.
Hasenhuttl added: "We are more than Danny Ings. It's a big loss but it's important now for other players to give us alternatives.
"Nobody has to play like Danny Ings, every player should play his best possible game."
The injury also rules Ings out of England's upcoming fixtures this month, with Gareth Southgate's side facing the Republic of Ireland in a friendly on November 12 followed by Nations League matches against Belgium on November 15 and Iceland on November 18.
Ings scored on his England debut last month in the 3-0 friendly win over Wales at Wembley.