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 will leave 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.
Meanwhile, Edinburgh centre Matt Scott has been ruled out of the remainder of Scotland's autumn Tests after tests showed he fractured a hand during Saturday's win over Japan.
The 23-year-old faces six weeks on the sidelines.
Scotland head coach Scott Johnson has called up seven players for Sunday's clash against South Africa at Murrayfield amid a number of other injury concerns.
Edinburgh quartet Jack Cuthbert, Tom Brown, Lee Jones and Ross Rennie come in, along with Glasgow pair Jon Welsh and Byron McGuigan and uncapped Leeds back Stevie McColl.