Arsenal defender Thomas Vermaelen will miss the rest of the season and team-mate Johan Djourou will be out for at least six weeks.
Vermaelen has been sidelined since September after picking up an Achilles injury during Belgium's Euro 2012 qualifier against Turkey.
He was initially only expected to be sidelined for a few weeks, but was forced to undergo further surgery on the problem in January.
A comeback this month had to be shelved and Arsene Wenger has now confirmed Vermaelen will play no further part in the current campaign.
"For Thomas Vermaelen the season is over," confirmed Wenger.
"In fairness he has not played since September, I never expected him to be fit before the end of the season.
"He is not out on the field yet and it is impossible [for him to play] after six months without competition. I am confident he will have a full recovery but for this season we cannot rely on him."
The centre-half is joined on the sidelines by Djourou, who suffered a dislocated shoulder during last week's FA Cup defeat at Manchester United.
The Swiss FA had suggested the injury was not as bad as first feared, but the defender is unlikely to be back until the closing couple of weeks of the season.
Wenger added: "Johan Djourou is out for at least six weeks.
"There's a little chance [he will play again this season], he has an arthroscopy on Monday and we will know more about the damage in his shoulder.
"We hope we will have good news but no matter what happens he will be out for six weeks."