Lee Byrne has been ruled out of Wales' autumn international campaign after suffering ligament damage in his right foot.
The Ospreys full-back limped off during Sunday's 32-32 Heineken Cup draw at Leicester with a recurrence of the injury which forced him out of the Lions tour of South Africa in the summer. He will be in plaster for six weeks before beginning a period of rehabilitation.
Wales will also be without the Ospreys lock Ian Evans, who has been sidelined for eight weeks after tearing his pec major tendon playing for Swansea against Pontypridd.
Wales' autumn campaign starts against New Zealand on November 7 followed by games on successive weekends against Samoa, Argentina and Australia.
Ospreys physio Chris Tower said: "Lee was reviewed by a specialist last night, and he had a scan which has revealed ligament damage in his right foot.
"The problem is a fairly subtle issue, 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."
Evans, meanwhile, had only just returned from 10 months out with a knee injury.
Tower added: "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."
Wales head coach Warren Gatland is already without props Adam Jones, who is recovering from a dislocated shoulder, and John Yapp with a torn bicep, while Duncan Jones is struggling with a groin problem.
Cardiff Blues lock Bradley Davies is also a concern after suffering a recurrence of a neck injury against Harlequins last weekend.
But Gatland has received better injury news from loosehead prop Gethin Jenkins and flanker Martyn Williams, who both underwent shoulder surgery after the Lions tour but are ahead of schedule in their rehabilitation.
Jenkins could feature for Cardiff Blues against Sale in the Heineken Cup on Friday night, while Williams is closing in on a return to action and could play some part in the November campaign.