Keith Andrews is out of the Republic of Ireland's opening Euro 2012 qualifiers with Armenia and Andorra after failing to recover from a groin problem.
The Blackburn midfielder's absence means it is likely that Derby midfielder Paul Green will make his competitive debut in Yerevan next Friday.
Andrews is Giovanni Trapattoni's preferred midfield option to partner Glenn Whelan, but his start to the season has been curtailed by this difficulty and he will remain in Lancashire for further treatment.
Trapattoni does have other options for a midfield role, with Derryman Darron Gibson top of the alternatives during the last campaign.
However, he has been dormant at club level this term, while Green — who burst onto the international scene in May — was given the nod for the recent friendly with Argentina when Whelan was sidelined.
There are still question marks over the availability of another intended starter, Liam Lawrence. He is back in training at Stoke after damaging his groin ahead of that Argentine encounter.
If he were to miss out then Birmingham's Keith Fahey would vie with Spartak Moscow new boy Aiden McGeady for a starting slot.
Keith Treacy impressed on the left side of midfield as a sub against Argentina, but his fitness is in doubt after he limped off in Preston's reverse to Sheffield United on Saturday.
Paul McShane missed Hull's loss to Doncaster with a calf problem so his participation is up in the air. He would most likely be a substitute in Armenia, though, with Sean St Ledger fit again to resume his partnership with Richard Dunne, with John O'Shea switching to right back. That said, O'Shea could be considered for the left back slot with Kevin Kilbane out of favour at Hull.