Henderson has been forced to undergo surgery on the problem and, while manager Jurgen Klopp is hopeful that his skipper will be available again before the end of the season, his absence further limits Liverpool's options at centre-back.
Virgil van Dijk, Joe Gomez and Joel Matip all remain long-term absentees who may not feature again this term, forcing Klopp to use his 18th different centre-back partnership during the derby defeat as Nat Phillips came on alongside Ozan Kabak.
January arrival Ben Davies is pushing for a first start given the dearth of other options, but Klopp may look to keep faith with Phillips and Kabak, despite the latter enduring his most difficult game yet against the Toffees.
Behind them, Liverpool could be without goalkeeper Alisson Becker following the news this week that his father tragically drowned in Brazil.
Klopp was understandably coy over the situation during his pre-match press conference and Liverpool will allow Alisson the chance to miss the game should he so desire.
If Alisson does choose to play then Phillips in for Henderson could be the only change Klopp makes to his XI, although there could be some important players returning to the squad too.
Diogo Jota is now back in training and should be in contention to feature, although any comeback appearance this weekend would most likely come from the bench after almost three months out.
Fabinho and James Milner are also due back in training on Saturday and so could be called upon if needed, but it is more likely that Klopp would give them a bit more time to recover from their respective muscle injuries.
Up front, Mohamed Salah will be looking to improve a record which has seen him score 16 goals in his last 17 away games across all competitions - as many as he had managed in his previous 51 such matches for the champions.
Liverpool possible starting lineup: Alisson; Alexander-Arnold, Kabak, Phillips, Robertson; Thiago, Wijnaldum, Jones; Salah, Firmino, Mane
Watch the Sports Mole Football Shorts prediction for this game below: