Wales flanker Dan Lydiate faces an extended spell on the sidelines after sustaining an anterior cruciate ligament injury, with Wayne Pivac forced to make multiple changes for Saturday's Six Nations match against Scotland.
Wales beat 14-man Ireland 21-16 on Sunday thanks to tries from George North and Louis Rees-Zammit but head coach Pivac will be without four of the players who started in Cardiff for the trip to Edinburgh.
There are fears that Lydiate, whose first Wales appearance in more than two years proved short-lived, could miss the rest of the season.
The 33-year-old, who is likely to be replaced by Josh Navidi, tweeted: "Always a massive honour and a privilege to pull on the famous red jersey even though it was short lived wishing boys best of luck for the rest of the @SixNationsRugby."
Wales assistant coach and defence specialist Gethin Jenkins said: "We watched Dan a lot over the Christmas period and he has been the in-form six in Wales.
"I am really gutted for him. It's a tough pill to swallow for him and for us as a squad."
Scrum-half Tomos Williams has a hamstring problem while centre Johnny Williams and winger Hallam Amos are both sidelined with head injuries.
No replacements have yet been named.
Pivac, who endured a miserable first year in the job, admitted the first major victory of his reign was tempered by a series of injury problems that left him "counting the walking wounded".
Scarlets centre Jonathan Davies will again be missing at Murrayfield as he continues to nurse an ankle injury and wing Josh Adams remains suspended following a breach of Covid-19 protocols.
To compound Pivac's midfield concerns, North scratched an eye against Ireland, while Nick Tompkins is thought to have a shoulder injury.
But British and Irish Lions back Liam Williams will be available after serving a suspension for a red card when playing for Scarlets against Cardiff Blues.
Wales have beaten Scotland 16 times in the countries' last 19 meetings, yet they will meet opponents in confident mood after a memorable Calcutta Cup win against England -- their first at Twickenham for 38 years.
"It's the same for them as it is for us," said Jenkins.
"When you win, you have got to back it up. You can't think you are top of the world, you've got to knuckle down and work on the stuff that got you that win."