Ireland will be without Jonathan Sexton and Mike McCarthy for their Six Nations trip to Scotland later this month.
Both players suffered injuries during their side's home defeat to England at the weekend, fly-half Sexton damaging a hamstring and second row McCarthy a knee ligament problem.
And team manager Mick Kearney has revealed neither will recover in time for the game at Murrayfield on 24 February.
He said: "Jonny's scan revealed a grade two hamstring injury. Progress has been good so far, but it's too early to say when he will return to play.
"Mike has hurt the medial ligament of his right knee. It's quite sore and he will be in a brace for two weeks. A further review will take place in two weeks."
The 12-6 defeat to England in Dublin ended Ireland's Triple Crown and Grand Slam hopes.