Wales centre Jamie Roberts has targeted an October return following knee ligament surgery on Thursday.
The Lion will miss the remainder of the season including the Blues Heineken Cup clash with Leinster and Wales' three-Test tour of Australia in June.
Roberts suffered a recurrence of a knee injury during the Blues' 31-3 Pro12 defeat at Glasgow last Friday.
"I'd miss September and hopefully aim to come back playing in October. That's a realistic goal," said Roberts.
"The decision has been made for me to have an operation on the anterior cruciate ligament later this week," he said.
"It will mean a minimum of roughly six months away from the playing field."
Roberts originally picked up a knee problem in the Heineken Cup win over Racing Metro in November.
He spent a further spell on the sidelines after suffering a knee injury during the Blues' 28-9 Pro12 win over Newport Gwent Dragons in December.
He returned for Wales' opening game of the Six Nations, the 23-21 win over Ireland in Dublin in February and played in the following four games as Warren Gatland's side secured the Grand Slam.
Roberts' absence is a blow to the Blues ahead of their Heineken Cup quarter-final against Leinster at the Aviva Stadium on Saturday with Dafydd Hewitt or Gavin Evans set to deputise.
And the news comes a day after the club sacked Gavin Henson for misbehaviour on a flight from Glasgow.
"First and foremost, I'm pretty devastated to be missing this weekend's Heineken Cup quarter-final match against Leinster, in what is our biggest match of the season," said Roberts.
"It's a match I've been looking forward to for a long time but unfortunately my body hasn't quite allowed me to be a part of such a huge occasion for us as a region.
"I originally injured my knee in Paris playing against Racing Metro after returning from the World Cup.
"With the fantastic help from the medical staff at the Blues and Welsh Rugby Union, I was able to rehab my knee well enough to get me through a handful of games for the Blues and the successful Grand Slam Six Nations campaign with Wales.
"However, following my injury in the match against Glasgow on Friday night I've been advised by the knee surgeon that my knee is now not stable enough to continue playing and potentially risk further injury to the knee.
"I suppose it's a chance for me to get my body fully right for what is a huge season for both club and country, with a certain carrot [the British Lions tour of Australia] at the end of it too."
"It will also allow me to continue my focus on the final year of my degree in medicine and the finals I'll be sitting next March."