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Mane's left leg buckled beneath him as he attempted to block a clearance from Everton left-back Leighton Baines shortly before the hour at Anfield.
After receiving treatment, he collapsed to the ground as he limped towards the touchline, before Divock Origi came on in his place.
Liverpool were 2-1 up when Mane left the fray, the Senegal international having broken the deadlock in the eighth minute with his 13th goal of the Premier League season.
Mane, 24, joined Liverpool from Southampton for a reported fee of £34 million ($42.7 million, 40 million euros) last June and has been one of their stand-out performers this season.
The match ended in Liverpool's favour, 3 -1.