Second-row forward Luke Charteris seems set to miss the forthcoming RBS 6 Nations Championship after suffering a knee injury while in action for his club Perpignan on Saturday
Reports in France say Charteris suffered ruptured medial knee ligaments during the Top 14 clash against Montpellier.
He is expected to be out for the rest of this season, effectively ending his hopes of making the British and Irish Lions squad to tour Australia next summer.
Wales interim head coach Rob Howley has already lost Scarlets fly-half Rhys Priestland and Ospreys prop Aaron Jarvis from his Six Nations plans.
Priestland suffered a serious Achilles tendon injury in a Heineken Cup game against Exeter earlier this month and he is unlikely to play again this term.
Jarvis, meanwhile, went off with a knee injury during the early minutes of Wales' defeat against world champions New Zealand last month.
And the Charteris setback continues an injury tale of woe for Wales.
Prop Adam Jones and flanker Dan Lydiate were ruled out of the entire autumn series of games against Argentina, Samoa, New Zealand and Australia, although Jones has recently started his comeback with the Ospreys.
Charteris' fellow lock Alun-Wyn Jones is currently sidelined with shoulder trouble, while Ospreys second-row Ian Evans has a knee injury and Cardiff Blues backs Jamie Roberts and Leigh Halfpenny are both also sidelined.
Wales kick off their Six Nations title defence against Ireland in Cardiff on February 2, then face a Paris appointment with France eight days later.