The Ospreys will have to go into their key home battle with ASM Clermont Auvergne in the second round of the Heineken Cup this weekend without Lee Byrne and Ian Evans.
Wales and British & Irish Lions full back Byrne looks set to not only miss this weekend's vital European clash, but also Wales' November internationals after damaging a ligament in his right foot.
Byrne picked up the injury in the Ospreys' 32-32 draw with Leicester Tigers at Welford Road in the Heineken Cup on Sunday. He will be in plaster for six weeks and then face a period of intensive rehabilitation.
"Lee was reviewed by a specialist last night, and he had a scan which has revealed ligament damage in his right foot," said Ospreys physio Chris Towers.
"The problem is a fairly subtle issue, however, with the nature of the ligaments involved, there is no quick fix and to rush him back would be counter productive in the long term.
"He is essentially looking at a period of rest, in plaster, for approximately six weeks, followed by a period of rehabilitation to get him up and running and back on the field."
And in another bitter blow to both the Ospreys and Wales, lock Ian Evans has been ruled out for at least eight weeks after tearing a major tendon playing for Swansea against Pontypridd in the Principality Premiership last weekend.
"Ian Evans has suffered a tear of his pec major tendon, and having discussed the injury with a specialist, he is provisionally looking at an eight week lay-off, based on our knowledge of previous injuries of this nature," added Towers.
Evans missed most of last season after having reconstruction surgery on his knee.
Finals Edition: Listen to the best guide to the European Rugby Cup Finals weekend in Dublin, which sees Leinster Rugby take on Stade Francais Paris at the RDS on Friday night in the Amlin Challenge Cup Final and then ASM Clermont Auvergne tackle Toulon in an all-French affair at the Aviva Stadium on Saturday.