Jurgen Klopp's plans for Saturday's visit of arch-rivals Manchester United were dealt a severe blow after Mane returned from Senegal duty with a hamstring injury which is set to rule him out for six weeks.
Liverpool are 13/8 with Sky Bet to win the huge clash at Anfield, with United also priced at 13/8 and the draw is 23/10.
The Reds, who are 28/1 for the Premier League title, have drifted slightly to 11/10 for a top four finish as they struggle to get their season firing.
Mane has established himself as a key player since his arrival from Southampton in the summer of 2016, scoring 13 league goals last season despite missing January because of the African Nations Cup and his campaign being ended in early April by a knee injury which required surgery.
The pacy forward scored in his first three Premier League matches before his sending-off at Manchester City and the subsequent three-match ban slowed his progress.
But his absence, which will see him miss matches against top-four rivals United, Tottenham and Chelsea, will still be keenly felt at Anfield at the weekend.
Salah, the club's leading scorer with six goals, told liverpoolfc.com: "I texted him when he was at the national (team) and then when he came back. He told me then he was injured, so that's bad news for everyone.
"But that's football and anything can happen. Now we have to focus on the game and keep moving forward."
In Mane's absence the obvious move would be to restore Philippe Coutinho to the wide left position he previously occupied before dropping into midfield to accommodate the two fast wingers.
Klopp would have breathed a sigh of relief to see the Brazilian and compatriot Roberto Firmino return from international duty in South America injury-free and the pair were both able to train on Thursday.
Fellow internationals Trent Alexander-Arnold, Joe Gomez, Marko Grujic, Ragnar Klavan, Simon Mignolet, Dominic Solanke and Georginio Wijnaldum also rejoined the main group.
Defender Dejan Lovren, who last month revealed he was not training properly and taking five pills before every match just to play through back and Achilles problems, is understood to be fine after returning on Wednesday having playing 90 minutes in Croatia's 2-0 World Cup qualifying win over Ukraine.
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