Mane’s absence is a huge blow ahead of their crunch clash with Manchester United on Saturday.
Liverpool could be without the Senegal star for a further eight games including clashes with Tottenham and Chelsea.
The 25-year-old picked up the injury while playing for his country in a 2-0 World Cup qualifying win over Cape Verde.
He returned to Merseyside on Monday and a scan has revealed Liverpool’s worst fears.
A club statement read: “The winger was substituted 89 minutes into Senegal’s 2-0 World Cup qualifying win over the Cape Verde Islands on Saturday.
“And it has now been confirmed that he picked up an injury during that fixture that could keep him out of action for up to six weeks.”
Mane has scored three goals in just four Premier League appearances so far this season.
He has already missed three league games due to a red card against Manchester City after kicking stopper Ederson in the face.
Mane – who scored 13 goals last season despite missing most of January at the Africa Cup of Nations – joins Adam Lallana on the treatment table.
Lallana this week travelled to Qatar to continue his rehabilitation from a thigh injury picked up before the start of the season.
Sergio Aguero has handed Manchester City a huge boost by returning to training ahead of schedule.
Aguero took part in a light training session just 11 days after breaking a rib in a car crash in Amsterdam.
He was expected to be sidelined for between three to six weeks.
A club spokesman said: “Sergio will build up his fitness in the coming days as he edges towards a first team return”.
Aguero is just one goal short of equalling Eric Brook’s all-time City record of 177.
