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.
The last five years have been an emotional rollercoaster on and off the pitch for RGC1404. Promotion to the Principality Premiership was the culmination of five years of hard work and investment in North Wales. WRU TV caught up with prop Joe Simpson, who was one of the first intake of WRU North Wales Academy players in 2010.
Ebbw Vale captain Damien Hudd picked up the biggest accolade of the night at the 11th Principality Premiership Awards Evening held at Principality Stadium, after leading his side to the title for the first time.
Wales assistant coach Robin McBryde is predicting a tough battle against England on Sunday despite the fact they may not be considered to be at full strength. Players will be out to impress Eddie Jones which makes England a dangerous proposition, he says.
Wales U20 captain Tom Phillips and performance psychologist Dr Rich Neil explain why spending three days at Monmouth RFC has further strengthened the togetherness of the squad ahead of the #WorldRugbyU20s