The Australian-born second-rower was stretchered off in the first half of Wales' scratchy 11-10 win over Fiji on Friday night. His hamstring was torn away from the bone in a sickening collision and he may not play again this season.
Wales coach Mike Ruddock confirmed: "The injury needs an operation and Brent is out of action for at least four months, possibly six.
"It's awful news for Brent and his family, as well as the Ospreys and Welsh rugby, who have lost a quality player.
"On the injury front, we are getting a lot more headaches than we would like."
Cockbain, who turns 31 on Tuesday, joins fellow British Lions Gethin Jenkins, Ryan Jones, Dwayne Peel, Tom Shanklin and Gavin Henson on Wales' ever-expanding injury list. As well, three other Wales players - Dafydd Jones, Kevin Morgan and Chris Horsman - limped off during the Fiji match with ankle injuries. Jones and Morgan are unlikely to play against South Africa next Saturday.
A special video package as Pontypridd claimed the double for the first time in their history by winning the Principality Premiership final, including match build-up, highlights, post match reaction and dressing room celebrations.