The Irish utility back was only just back in action for Munster after World Cup duty but had to helped off the Aviva Stadium.
He will now miss Munster's Heineken Cup double header against Northampton and Castres but could be back in time for the Boxing Day derby clash with Connacht.
A Munster statement said: "Keith Earls had a scan yesterday in Limerick that confirmed he has sustained medial ligament damage and will be out of action for four to six weeks."
The news will come as a blow to coach Tony McGahan, who would have been hoping Earls could continue his recent international form for a Munster side that have won just one of their last four matches.
The utility back was one of Ireland's standout performers at the World Cup, playing in every match and ending the tournament as the side's top try scorer with five touch downs.
Earls' injury could give one of Munster's promising youngsters his chance on the European stage, with 22-year-old Danny Barnes looking most likely to get the call up after coming off the bench to replace Earls on Friday.
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