Adam Jones and Jonathan Davies have been ruled out of Wales' three remaining autumn Tests due to injury, the Welsh Rugby Union has announced.
Prop Jones will miss the matches against Argentina, Tonga and Australia after suffering a calf injury during Saturday's defeat to South Africa at the Millennium Stadium.
Centre Davies, as expected, will also sit out those games after tearing a pectoral muscle in the 24-15 loss to the Springboks.
Davies, who on Tuesday it was announced would be leaving Scarlets for French club Clermont Auvergne next summer, is set for an operation later this week and could be out of action for up to four months, making him a doubt for the start of the RBS 6 Nations.
And his absence comes with his midfield colleague Jamie Roberts already sidelined for the autumn matches with an ankle injury, while prolific try-scoring wing Alex Cuthbert is also recovering from ankle trouble and looks set to be unavailable to Wales coach Warren Gatland until the Six Nations starts in February.
Jones, one of the most destructive scrummagers in world rugby, limped off after 10 minutes against South Africa.
He was one of four players who made premature exits due to injuries in that game and, like Davies, he leaves a huge void to fill.
Bath forward Paul James went on for Jones at tighthead three days ago and, even though he is a loosehead specialist, it would be no surprise if he continues in the number three shirt against Argentina on Saturday.
Gatland is due to name his team for the Pumas encounter on Thursday and he has already drafted four players into his training squad - Scarlets props Samson Lee and Rhodri Jones, together with Newport Gwent Dragons backs Tom Prydie and Hallam Amos.