Wales face injury crises in the front and back rows for their November Tests, which include matches against New Zealand, Argentina and Australia.
Cardiff Blues prop Gethin Jenkins and flanker Martyn Williams are both to undergo shoulder operations after returning injured from Lions duty.
Blues coach Dai Young revealed neither of the experienced forwards will be available until at least November.
Prop Adam Jones (shoulder) has already been ruled out of the autumn Tests.
Osprey prop Jones and Jenkins - with a fractured cheekbone - were both forced off early in the second half of the Lions' second Test against the Springboks.
But Young revealed that Jenkins had actually dislocated his shoulder in an earlier tackle and played on through the pain.
Williams picked up a shoulder problem early in the Lions tour but recovered sufficiently to start four matches in all, including the victorious final Test in Johannesburg.
But he will have surgery next week and, like Jenkins, faces four months on the sidelines.
Williams' absence is likely to give coach Warren Gatland his biggest selection problem with no obvious replacement.
606: DEBATEWilliams' Blues understudy Robin Sowden-Taylor wore the number seven jersey for summer tour Test wins against Canada and United States.
But after his arrival in the job, Gatland was so concerned at the lack of Welsh depth in the specialist open-side position that he persuaded Williams to come out of the retirement he announced after Fiji knocked Wales out of the 2007 World Cup.
Another Blues back-rower - ex-Wales Under-20 captain Sam Warburton - is also a contender for the autumn Tests, but his opportunities at senior level have been limited by injuries.
The absence of Jenkins leaves Gatland with another headache at loose-head.
The Wales coach is likely to choose between the Ospreys' Duncan Jones and Blues' John Yapp, while Jenkins was also able to cover the tight-head position.
One contender for that role will be Sale's Eifion Lewis-Roberts, who was recalled for Wales' summer tour to north America, but had to pull out with injury.
In his absence, Duncan Jones stepped into the unfamiliar tight-head berth in the wins against United States and Canada .
Neath's Craig Mitchell, who is also on the Ospreys books, did duty from the bench, Wales having overlooked Scarlets' summer recruit Rhys Thomas for the tour.
Blues boss Young is already without centre Tom Shanklin, who suffered a shoulder injury that forced him to miss the Lions tour, and wing Tom James - who suffered a similar blow on Wales' summer tour - for the start of the season
"We've got a number of injuries, probably more so than we did this time last year, which is unfortunate," Young said.
"Tom Shanklin, as we know, had a shoulder operation so he won't be ready for the start of the season.
"Tom James has had a shoulder operation - there's a lot of shoulders [injured] and obviously he'll be out until October-ish as well.
"We've got a number of players out, but I'm confident in the squad.
"As one door shuts another opens to give people opportunities within the squad. But it's fair to say we certainly don't want to pick up many more injuries before the season starts.
"It's uncanny really, but they're all rugby injuries, not training injuries. They're all game injuries so you can't do anything about that.
"That's one of our goals through pre-season, that we don't pick up any training injuries and we feel that's a massive goal.
"In the early part of the Heineken Cup there may be one or two players missing, but we've recruited well.
"We've got a 36-man squad, but a 36-man squad full of quality so we're looking forward to it and confident we can have a good season."
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