Dan Lydiate will miss the rest of the season after suffering a serious knee injury on his first cap for Wales since 2018.
Scans have shown the Ospreys flanker injured his anterior cruciate ligament on his comeback for Wales against Ireland in the Six Nations.
Lydiate has been released from the Wales squad and will be monitored by WRU and Ospreys staff in his recovery, as he faces a lengthy lay-off from rugby at a time when he had returned to hot form to be capped.
The match at the Principality Stadium had been Lydiate's first involvement with Wales since facing Australia in November 2018.
A WRU statement read: “Dan Lydiate has been released from the Guinness Six Nations squad due to an anterior cruciate ligament injury sustained in the match against Ireland at Principality Stadium.
“He will undergo a number of assessments and consultations in the coming days to establish the best course of management.”
The 21-16 win over 14-man Ireland may have Wales off to a winning start in the Six Nations, but they lost a further three players to injury.
Scrum-half Tomos Williams (hamstring), centre Johnny Williams and wing Hallam Amos (both concussions) have all been ruled out of Wales' round two fixture against Scotland through injury.
The statement added: “Tomos Williams suffered a hamstring injury in the game against Ireland and is currently being assessed. He is ruled out of the fixture against Scotland on Saturday.
“Johnny Williams and Hallam Amos will both miss the fixture against Scotland on Saturday due to head injury.
“Player call ups will be made and announced in due course following COVID-19 testing and results.”
Wales' last trip to Murrayfield in the corresponding fixture in 2019 saw Josh Adams and Jonathan Davies tries nudge Warren Gatland's men to a 18-11 victory, en route to the Grand Slam.
Head coach Wayne Pivac will remain without Adams for this weekend's clash due to the ban he will serve for breaching team protocols to attend a gender reveal party.
