The 2009 Lions tourist limped out of his country's defeat to New Zealand last weekend with a knee injury.
Worsley has since had a series of scans on the problem which have revealed Medial Collateral Ligament (MCL) damage to his right knee.
The 32-year-old London Wasps star will now see a surgeon but neither Wasps nor England are able to say how long he could be sidelined for.
The World Cup winner had only just returned to the England starting line up having missed the loss to Australia through injury and then been among the replacements for the narrow win over Argentina.
"After leaving the field on Saturday as part of the England side that faced New Zealand at Twickenham, Joe Worsley has undergone scans which indicate a Grade 3 Medial Collateral Ligament (MCL) injury," said a statement from the Adams Park club.
"Joe will now see a surgeon to discuss the best possible management for his injury but no time frame can be given at this stage."