Captain Craig Bellamy is out of Wales' Euro 2012 qualifiers against Bulgaria and Switzerland next month.
Bellamy, currently on-loan at Cardiff from Barclays Premier League side Manchester City, has been sidelined for three weeks with a knee problem that has hampered him throughout his career.
Bryan Flynn, caretaker boss of the national side, confirmed that Bellamy would miss the forthcoming qualifiers.
"Craig will be unavailable for the two matches next week" Flynn told BBC Sport Wales.
"I had a really long, excellent conversation with Cardiff manager Dave Jones just over 10 days ago...and we made the decision that Craig will not be available due to his fitness.
"He has an ongoing knee problem and hasn't played for the last five games.
"Obviously we've been aware of that and unfortunately for Craig and for us he won't be able to put on a red shirt next week. It's a big disappointment for me as caretaker manager. I wanted Craig in the team but these things happen."
Wales lost their opening Group G game against Montenegro and face Bulgaria at the Cardiff City Stadium on October 8, followed by Switzerland in Basle four days later.
The defeat to Montenegro saw John Toshack depart as manager and Wales Under-21 coach Flynn appointed on a caretaker basis in his place.