Defender Dylan Lawlor will miss Wales' final two Nations League matches against Norway and Portugal with a hamstring injury.
The 20-year-old suffered the setback playing for Cardiff City against Watford earlier this month, having only just returned from a knee issue which kept him out of the start of the season.
He has now been ruled out until after November's international break.
"It's naturally very disappointing," said Bluebirds head coach Brian Barry-Murphy.
"He's put so much work into coming back from his knee injury that he suffered so long ago.
"But this gives him a chance to do his rehabilitation properly with no rush and make sure that when he comes back, he's good to go again."
Lawlor has not played for Wales since suffering the original problem during the 1-1 draw with Ghana in June.
He made his first start of the season at Blackburn on 10 October, before suffering his hamstring issue just three days later.
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When asked if he regretted playing the defender in Cardiff's games against both Blackburn and Watford after such a long spell out, Barry-Murphy said "a little bit".
Speaking prior to Cardiff's Championship match against Birmingham on Saturday, Barry-Murphy revealed Lawlor is expected to be out for around five to six weeks.
"Hindsight is an easy thing but he did a really good job against Blackburn," the Irishman added.
"We wanted to give him some consistency and we needed him really so we were limited in what options we had.
"It is what it is now we have to just move forward."
Wales play Norway in Oslo on 14 November before hosting Portugal in Cardiff three days later.
Craig Bellamy's team still have a chance of avoiding relegation from League A and securing a Euro 2028 qualification seedings boost.
"I think the positive is that his knee hasn't been pain free since the Ghana game for Wales," Barry-Murphy added.
"So even though when he came back against Blackburn he still had some pain in it and in the game against Watford where he got injured he wasn't totally pain-free or comfortable.
"So this five or six week period, however long it is, gives us a chance to really protect his knee, strengthen it and make sure that when he does come back from this and his hamstring injury that he now has, he's in a very positive position to be fit for the remainder of the season."