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.
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
Midfielder Fabinho can also deputise at centre-back, as he did 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.
BBC Sport’s Simon Stone
This is truly terrible news for Liverpool.
The Premier League champions may not be putting a timescale on Virgil van Dijk’s likely absence but in the short term, they don’t really have to.
Few players have returned from cruciate ligament surgery within six months – and depending on the exact extent of the damage, it could be longer.
Even a six-month absence would keep Van Dijk out until the back end of April. Effectively, it means Jurgen Klopp will have to do without his defensive talisman and 2019 PFA Player of the Year for the rest of the season.
It will stretch Liverpool’s defensive resources – and Joel Matip and Joe Gomez have a big job ahead of them in a season in which the physical demands will be like no other given the reduced amount of time the campaign is being played over.
The news will frustrate Liverpool even further because Everton keeper Jordan Pickford escaped punishment for the terrible tackle that inflicted the damage. Liverpool did not even get a free-kick.