Ospreys and Wales flanker Dan Lydiate has been ruled out for the rest of the season with a biceps injury.
Lydiate, 30, was replaced in Ospreys' 22-9 away win against Dragons and will have surgery later this week.
It is a blow for Wales who are already without Sam Warburton, while number eight Taulupe Faletau is doubtful for the start of the Six Nations.
"The decision has been taken in Dan's best interests to undergo surgery," said the Ospreys.
Wales are due to name their squad for the Six Nations on Wednesday, 17 January and open their campaign at home to Scotland on Saturday, 3 February.
The Ospreys face crucial European Champions Cup matches against Saracens and Clermont Auvergne in the next two weeks.
It is also a major setback for the player, who missed most of last season and the start of the 2017-18 campaign following a knee injury suffered in Wales' 27-13 win against South Africa in November 2016.
Wales head coach Warren Gatland has a number of back row concerns before the Six Nations.
Warburton is already ruled out for the rest of the season while Bath's Faletau is recovering from a knee injury.
Gloucester's Ross Moriarty, who deputised for Faletau last season, has missed the bulk of this season with a back injury, but has returned to training.
Gatland also has issues behind the scrum as centre Jonathan Davies is out for the season and Dragons wing Hallam Amos suffered an ankle injury in the Christmas derby match against Cardiff Blues.
Saracens back Liam Williams is sidelined with a groin injury, and has not played since Wales' win over Georgia in November.
Source: BBC Rugby Union News