Jenkins, a Lions tourist in 2005 and 2009, is due to undergo surgery on a toe problem which has been cause of his troublesome calf injuries.
He was limited to just one start in last year's Six Nations and made just four international appearances in 2010.
The 30-year-old is sidelined until April though Wales hope the operation will at last see him injury free for the World Cup in September.
"It's a big blow for Wales and ourselves," Cardiff Blues director of rugby Dai Young.
"No one wants him to miss the Six Nations but it's better for him to have the operation now and be back before the end of the season in time for Wales' warm up matches in the summer and the World Cup.
"Wales and ourselves have gone down every path, reducing his training and giving him longer rest periods because he wanted to avoid having an operation. But we have got to a stage where surgery the only feasible option.
"He's been frustrated because he hasn't been able to do the fitness work and training he would have liked and he feels it's affecting his game.
The news will be a major set-back to Warren Gatland's Six Nations plans, having formed a fearsome front-row with fellow Lions Adam Jones and skipper Matthew Rees. Ospreys prop Paul James is now set to face England in the Championship opener on February 4 and Young believes the Ospreys man is up to the job.
"Paul is important, he's done really well for the Ospreys and Wales. From Gatland's point of view he wants everyone available for the World Cup and Gethin's injury will give the likes of Paul more experience.
"It's important that we get Gethin back because we all know what he can do when firing on all cylinders."