Johnny Sexton has been ruled out of Ireland’s RBS 6 Nations opener against Scotland after failing to shake off his calf problem.
Flanker Peter O’Mahony will also miss the Scotland clash after suffering a hamstring strain, but Ireland will feel the loss of linchpin fly-half Sexton most acutely.
Paddy Jackson should now start at fly-half in Edinburgh, while late squad addition Ian Keatley could be eyeing his first Test action in almost two years off the bench.
Uncapped Munster centre Rory Scannell is the only other recognised option at fly-half, with Ireland again defending the decision to overlook Bordeaux’s Ian Madigan.
“We felt it right not to push him through the week and risk potential further damage,” said Ireland forwards coach Simon Easterby of Sexton.
“He’s obviously had a lot of lower limb injuries, a hamstring injury which we’ve managed with Leinster in the pre-Christmas period.
“As a result of his calf strain and the fact we don’t want to compromise his calf any further, we feel it best to leave him out this week and make sure he’s right for upcoming games.”
Sexton suffered his latest injury blow in Leinster’s 24-24 European Champions Cup draw at Castres on January 20.
The 31-year-old limped out of the first half of Leinster’s draw in France, detecting the calf issue himself with his provincial bosses hoping a quick withdrawal would boost his chances of being fit to start the Six Nations.
Ireland expected Sexton to return to full training on Tuesday, and had banked on the 63-cap playmaker winning his fitness battle to face the Scots.
Now Ulster’s 25-year-old Jackson will step up into Ireland’s number 10 shirt, having run the backline operations throughout training last week.
Leinster’s Joey Carbery remains sidelined after ankle surgery, with the 21-year-old’s absence further thinning Ireland’s options at 10.
Ireland bosses continue to favour home-based stars for Test match selection, with head coach Schmidt happy to follow that general directive.
While 19-cap Jackson has the experience to cope with the starting jersey, Keatley boasts just four caps - and has not featured since Ireland’s 26-3 win in Italy on February 7, 2015.
And forwards coach Easterby insisted Madigan would have been a tricky selection option for the Six Nations’ first two rounds, having been required for Bordeaux duty last weekend.
“What’s the alternative? Is he the first choice for Bordeaux?” said Easterby, of Madigan and Ireland’s selection options at fly-half.
“Unfortunately he couldn’t be with us last weekend anyway because he was on the bench for Bordeaux against Clermont. So it compromises his position with us when he’s not playing in Ireland.
“We’re trying to support the guys who are staying here and on the whole that will be the case.”