Mane's finishing and pace have been key for Liverpool under Klopp and the team won just one of seven games in January -- their worst run of results all season -- when Mane was at the African Nations Cup.
"Pretty sure Mane needs surgery and then it is season over. Impossible that he will play again this season," Klopp told a news conference.
Klopp also said midfielder Philippe Coutinho and striker Daniel Sturridge were doubtful for Saturday's league visit to Stoke City while English duo Jordan Henderson and Adam Lallana will both definitely miss the game.
The German, however, said he would not dwell on either the injury crisis or how Liverpool's rivals were doing in the race for the top four, and urged his players to focus on picking up points.
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"It's not about thinking about the players you can't (select), it's about thinking of the players you can," Klopp said.
Liverpool, who drew 2-2 with Bournemouth in midweek, are third in the table on 60 points, six points above fifth-placed Arsenal and sixth-placed Manchester United, having played two games more than both.
"We want to qualify for the Champions League," Klopp added. "We don't play any of our rivals any more so we can't influence them. We just have to get as many points as we can.
"I don't think 60, or 62, or 65 points will be enough to reach the Champions League. We need to collect a few more points."
(Reporting by Hardik Vyas in Bengaluru; editing by Martyn Herman and Toby Davis)
