Liverpool centre-back Virgil van Dijk needs surgery on a knee ligament injury sustained in the 2-2 draw at Everton on Saturday.
The 29-year-old Netherlands defender was unable to continue following a rash challenge by Toffees keeper Jordan Pickford in the first half.
It is unclear how long he will be out for with the anterior cruciate ligament (ACL) injury, reports the BBC.
He went for a scan before a specialist confirmed the extent of the damage.
Returning to action after ACL surgery can take many months.
Van Dijk has been a key figure for Liverpool since signing for them in January 2018 for £75m.
He has played every league game for the club in the past two seasons as Liverpool finished second in 2018-19 before winning their first top-flight title in 30 years in 2019-20.
The Dutchman was also a leading figure for the side as they won the Champions League in 2019 and Club World Cup later that year.
He had played seven times for the Reds this season prior to the Merseyside derby.
Van Dijk’s absence will leave manager Jurgen Klopp with Joe Gomez and Joel Matip as his main centre-backs as well as the inexperienced Nathaniel Phillips.
Gomez and Matip have never started a match together as centre-backs for Liverpool. Before Saturday’s Merseyside derby, the last time they both played in that position for any part of a game was the last hour of the 4-1 defeat by Tottenham in October 2017 at Wembley
“It’s huge because of the quality that he brings to Liverpool on the pitch and in terms of his organisational skills,” former Liverpool defender Stephen Warnock told BBC Radio 5 live.
“When you look at the the central-defensive positions at Liverpool – Joel Matip and Joe Gomez have also had injury problems. Who are the other replacements behind that? Fabinho is who they usually turn to. It will definitely hinder Liverpool’s defence of the title.”
Midfielder Fabinho deputised at centre-back in the win at Chelsea earlier this season.
In addition to Liverpool, the Netherlands will be keeping their fingers crossed he will be fit to take part in the postponed Euro 2020, which is now set to take place from 11 June to 11 July 2021.