James McCarthy and Glenn Whelan have both been ruled of the Republic of Ireland's crucial Euro 2016 qualifier with Scotland in Celtic Park on Friday.
McCarthy had been a doubt for the Group D game all week after he picked up a hamstring strain during Everton's 1-1 draw with Sunderland last weekend.
The midfielder underwent a scan on the injury on Wednesday and while there was hope that he would be fit, it has now been confirmed that he will now miss Friday's game.
The game comes just too early for Whelan, who continues to recover from a fractured leg he suffered in Ireland's 1-1 draw with Germany last month.
Whelan had trained with the squad throughout the week but manager Martin O'Neill has decided not to risk him in Glasgow.
It is not yet known whether O'Neill will call up any replacements for the midfield duo.
Meanwhile, Scotland's Crystal Palace midfielder James McArthur is out with a calf injury.
