Aaron Ramsey will miss Wales' opening World Cup qualifier against Moldova.
Ramsey suffered a hamstring injury in Arsenal's Premier League opener against Liverpool, and Gunners boss Arsene Wenger said he would not be fit until after the international break.
Wales manager Chris Coleman, naming his squad for the Moldova game in Cardiff on September 5, said he expected Ramsey to be out for another three weeks.
Coleman said: "When you've got a player as good as Aaron, take him out of any team and you are going to know about it.
"He is irreplaceable, he makes a huge impact for us. He is a great player and it's a shame he's not here. He's a loss to any team."
Wales show three changes to the squad which reached the semi-finals of Euro 2016 this summer.
Jonathan Williams is expected to be out for a couple of months after suffering an ankle injury in a Crystal Palace pre-season friendly, while veteran Nottingham Forest midfielder David Vaughan has announced his retirement from international football.
"Jonny has had a good impact on the team and brings something different," said Coleman.
"I saw that tackle on him, it was a coward's tackle from behind, and that was annoying.
"Vaughny sat down with me when he got back from France and explained he was going to retire.
"I tried to talk him out of because he's been with us for so long and he's got good quality.
"But he wants to spend more time with his family and concentrate on his club career, and we've got to respect that.
"He's been a great servant for Wales."