Shay Given will not add to his 125 caps after announcing his retirement from international football ahead of the Republic of Ireland's friendly with Serbia tomorrow.
The Aston Villa keeper was already missing from the Irish squad after manager Giovanni Trapattoni opted to rest a group of senior players who were involved in Euro 2012.
But Trapattoni has since seen his squad hit by withdrawals.
Stephen Ward and Keith Treacy have joined a growing casualty list ahead of the Serbia game.
Wolves defender Ward and Burnley midfielder Treacy have returned to their clubs after being diagnosed with knee and groin injuries respectively.
On Sunday it was determined Wolves striker Kevin Doyle and Stoke defender Marc Wilson were not fit to link up with the squad.
Doyle withdrew with a haematoma, an infected bruise, due to the risk of deep vein thrombosis associated with air travel, whilst Wilson was diagnosed with a potential virus.
Added to the earlier withdrawals of Sean St Ledger (knee), Darron Gibson (thigh) and Wes Hoolahan (Achilles) - the latter pulling out a few hours after his selection - the build-up to the game in Belgrade has not been an easy one for Trapattoni.
When announcing the squad last month Trapattoni took the decision not to include senior figures Robbie Keane, Richard Dunne, Damien Duff, Stephen Hunt, Keith Andrews and Given.
Given has since decided to quit the international scene, saying: "This has been an extremely difficult decision for me to make.
"I have dedicated 16 years of my life to my country, and I have a great affinity with Giovanni Trapattoni's squad.
"I'd like to thank the Giovanni, (assistant) Marco (Tardelli) and Alan Kelly for their support during my time with the team. I will continue to be Ireland's biggest fan, and wish the lads well as they embark upon their new campaign."
It is understood there was a gentleman's agreement the group of senior players would not be included after their participation in Euro 2012.
However, except for Given they will all certainly come under consideration for the opening match of the Republic's World Cup qualifying campaign in Kazakhstan on September 7.
For now the Republic will look to put behind them a disappointing Euro 2012 with a warm-up against a Serbian team who have lost six of their last eight matches, albeit with every game on the road.
With so many senior figures either absent or injured, it falls on a number of the younger players to instil some much-needed vigour into proceedings.
For Wigan midfielder James McCarthy, Everton defender Seamus Coleman and Sunderland striker James McClean, with just six appearances between them, it is their chance to prove a point.
Assistant manager Marco Tardelli said: "For this game with Serbia we wait for the players to show us they are ready to play in an international match.
"It's not a worry we have so many players missing. I am sure the players with us will show they are ready to play.
"They have good motivation to play and the young players can give us a strong, physical side, and they can show us they can stay in the squad."