Owen Watkin is likely to miss the start of Wales' Guinness Six Nations title defence with a knee injury, while Ospreys team-mate Gareth Anscombe has undergone a second operation on the issue that ruled him out of the World Cup.
Centre Watkin could be sidelined for up to eight weeks after having surgery on an injury he picked up against Racing 92 earlier this month, with Wales set to host Italy on February 1 before heading to Dublin to take on Ireland a week later.
"A small cartilage tear was confirmed and surgery to deal with the tear was deemed to be the best course of treatment for Owen," read a statement from the Ospreys' medical team.
Watkin's potential absence comes as another blow to new Wales head coach Wayne Pivac ahead of his maiden Six Nations campaign, with fellow centres Jonathan Davies and the uncapped Willis Halaholo already ruled out.
Fly-half Anscombe played no part for Wales in Japan after injuring his knee in their opening World Cup warm-up game against England in August.
"Gareth has undergone a second procedure to his right knee this week," added the Ospreys' statement.
"As a result of Gareth's progress plateauing in the last month, and in conjunction with Gareth and his specialist, it was decided that a secondary minor procedure would be in his best interest, with the aim to allow him to progress and accelerate his rehabilitation in the new year.
"Surgery went well and at this stage we're ruling nothing out with regard to a possible return towards the end of the season, however we'll be in a better position to clarify a realistic prognosis in the new year when he goes back to see the specialist."