Wales midfielder Joe Allen will miss the World Cup qualifier against the Czech Republic after picking up an injury in this week's 3-1 defeat to Belgium, caretaker boss Robert Page confirmed on Friday.
Allen, 31, limped off only seven minutes into the match against Group E favourites Belgium on Wednesday -- a miserable return to international action for the influential player.
Allen, who had not played for Wales since 2019 after suffering an Achilles injury, was one of their star performers as they reached the Euro 2016 semi-finals.
"We've lost Joe, which is a shame," said Page. "It is a big loss for us. It's disappointing not to have him. He'll have to go back to the club (Stoke) now and they'll assess him."
Wales play a Cardiff friendly against Mexico on Saturday while the Czechs, 6-2 winners away to Estonia in their opening qualifier, are at home to Belgium. Wales host the Czechs on Tuesday.
Only the group winners progress automatically to the finals in Qatar in 2022.
Page will also be without defenders Ben Davies, Tom Lockyer and James Lawrence for the next two games.
Charlton full-back Chris Gunter will lead the side out against Mexico, becoming the first Welshman to win 100 caps.
"He's a model professional and thoroughly deserves 100 caps and all the credit he will get for having achieved that," said Page.
"It's good to be a part of that with him. He's a good lad, certainly one of the people you want to see in the game do well."
Gunter, who made his debut in 2007, has endured highs and lows in his international career.
The death of Wales manager Gary Speed in 2011 left deep scars on a young squad but they went on to reach their first major tournament for 58 years -- Euro 2016.
Gunter said the run to the last four in France would remain with him for the rest of his life.
"We were so close as a team, squad and staff. It was really special as we'd gone through some tough times together," he said.
"To then achieve something like we did... knowing how much it meant to everybody. When you've had tricky times it obviously means a lot more."