Virgil Van Dijk's dreaded need for cruciate surgery was confirmed after a horror tackle from Everton goalkeeper Jordan Pickford at the weekend, but what does it mean for their defence?
What shape does their backline take on now that the Dutchman is likely out for the season?
And will his absence have an impact on the title race?
We got the views of Liverpool and Republic of Ireland legend Mark Lawrenson, as well as our own Premier League pundits Nathan Murphy and Phil Egan:
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MARK LAWRENSON:
How big a blow is it for Liverpool?
"He's probably the best defender in the world, I can't really think of anyone else that would be up there with him. Not only is he an outstanding player, but the effect he has on people around him... He's probably played with four or five other Liverpool players alongside him in central defence and he just made the whole thing look so easy.
"His passing, his threat at the other end in terms of scoring goals from set-pieces, he's a very, very good leader."
How should Liverpool's defence look without VVD?
"I thought Matip was quite good at the weekend so Klopp might have to go [with] Matip and Gomez. I think the problem with Joe Gomez a little bit is Trent Alexander-Arnold obviously loves to get forward all the time.
"Gomez is still relatively inexperienced, and when Trent goes forward does he get pulled out a little bit? But I'd go with him - Gomez and Van Dijk was very good, Gomez just hasn't started the season well, but neither has Trent.
"Fabinho can go in and play there but long-term? I'd be more inclined to go Gomez and Matip."
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NATHAN MURPHY:
How big a blow is it for Liverpool?
"There's no getting away from how big a setback Van Dijk's injury is for Liverpool, he has been without doubt the single most important player in Liverpool's recent history and arguably the most transformative player in the Premier League in recent seasons."
How should Liverpool's defence look without VVD?
"I can't see Liverpool playing Fabinho at centre-back on a regular basis so it will fall on Matip and Gomez's shoulders to get them through to the January transfer window. All three have shown signs of real quality in recent seasons but the concern for Liverpool is how much of that is down to playing alongside Van Dijk?"
Will Van Dijk's absence impact the title race?
"Something that may benefit Liverpool is the crazy nature of this Premier League season. Every team is conceding goals so are defences as important as previous seasons?"
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PHIL EGAN:
How big a blow is it for Liverpool?
"Van Dijk has been an ever present for Liverpool since he signed for the club in January 2018 and he has transformed the team since then. They wouldn't have reached two Champions League finals and won a Premier League title without him.
"Not only is he an exceptional defender, but he also is an organiser and has the ability to hit long range passes. He brings a calmness at the back, which was not the case before he signed for them and it was quite evident on Saturday after he went off how much more vulnerable Liverpool were from set pieces. Michael Keane doesn't score that goal if Van Dijk is there and he has always posed a massive threat in the opposition penalty area."
How should Liverpool's defence look without VVD?
"Ideally Klopp would like to play Joel Matip and Joe Gomez but the reality is Matip is injury prone so won't be reliable enough and Gomez has shown recently that he has off days, as was the case at Villa Park.
"Liverpool have kept one clean sheet in the league this season and that was with Fabinho playing alongside Van Dijk away to Chelsea so the Brazilian will surely have be used in defence more often.
"Jordan Henderson could fill the void left by Fabinho in midfield as he did so well last season when Fabinho was injured. Liverpool were already short of options in central defence when they sold Lovren so we could see a throwback to a few years ago when Jurgen Klopp's side were involved in some pulsating games because they leaked a few goals."
Will Van Dijk's absence impact the title race?
"It's all about staying in touch with their rivals until January when they can bring in another defender, but the early indications are that all the top teams will drop points."
