Cardiff centre Willis Halaholo has been ruled out of Wales’ summer tour to South Africa due to a hamstring injury.
Scrum-half Tomos Williams (hand) and wing Josh Adams (knee) are also battling to be fit to face the Springboks in a three-Test tour in July.
Wales head coach Wayne Pivac names his squad later this month.
He is already without Ken Owens, Leigh Halfpenny, Justin Tipuric and Aaron Wainwright.
Other injury doubts include Johnny McNicholl, Wyn Jones, Ross Moriarty and Leon Brown, while Dragons duo Will Rowlands and Elliot Dee have also recently been sidelined.
Wales play three Tests against the Springboks, beginning on 2 July in Pretoria before games in Bloemfontein and Cape Town on successive Saturdays.
Halaholo, 31, made his Wales debut against Scotland in 2021 and has played 10 internationals.
Cardiff director of rugby Dai Young said: “Willis is definitely a non-starter (for South Africa).
“He had a real nasty hamstring tear but also had his shoulder done. His shoulder was probably something we would have looked at later.
“Because his hamstring was nasty with tendon involvement, that was always going to rule him out of the summer tour, it made sense for him to get his shoulder done at the same time.
“It is touch and go for Josh and Tomos, they are not available for the next two games for us.
“I am sure the Welsh management will pick up with our medical team to see where they are.
“They are definitely not ruled out or ruled in but it’s touch and go on how they respond to early stages of rehabilitation over the next couple of weeks.
“Josh suffered a medial (knee) ligament injury so he has started his first stages of his rehabilitation.
“It just depends how quickly that comes on and where he us over the next couple of weeks, and Tomos is very similar.
“We will get to a point where the two medical teams will chat and it’s over to Wales on whether they are comfortable in their timescales.”