Robbie Henshaw, Josh van der Flier and Devin Toner are facing a battle to make the Heineken Champions Cup quarter-final against Ulster at the end of the month.
All three have been ruled out of this Friday night's Pro14 trip to Edinburgh, and are now in a race to make Saturday week's European showdown at the Aviva Stadium.
Henshaw continues to struggle with the dead leg that cut short his Six Nations. Van der Flier (groin) missed Ireland's dreadful showing in Wales while Toner hurt his ankle in the opening-tournament clash with England and required surgery.
In better news, Dan Leavy is in line for his first appearance of the year. He's been out with a calf problem since before Christmas but the flanker is back in the fold and ready to play.
Luke McGrath (knee), Joe Tomane (hamstring) and Nick McCarthy (foot) are also back for Leo Cullen.
Tomane and McCarthy have been out of action since November while McGrath picked up a knee ligament injury in January’s Heineken Champions Cup clash with Toulouse.