Ireland captain Johnny Sexton, halfback Conor Murray and lock James Ryan have been ruled out of Monday's (NZ time) Six Nations clash with France in a massive setback to coach Andy Farrell, as he seeks to keep his side's tournament hopes alive.
Sexton and Ryan - two of Farrell's most important players - were replaced with suspected concussions during last week's opening 21-16 loss to Wales. Ireland played most of the game with 14 men, after Peter O'Mahony's 14th minute red card.
Murray's injury paves the way for Kiwi Jamison Gibson-Park to start in the No.9 jersey. The former Māori All Blacks halfback made his debut late last year and will make his first start against the French, alongside replacement first-five Billy Burns.
The 28-year-old former Blues back qualifies for Ireland through the three-year residency rule, after moving north to play for Leinster in 2016.
Ulster first-five Burns made a costly error in the final seconds in Cardiff, when he attempted to kick for an attacking lineout five metres out, but booted the penalty too long.
The lack of top-level back-up made Sexton's return much more critical. Ulster's Iain Henderson ably filled the big hole left by Ryan last Monday and will captain the side for the first time, while in-form Rhys Ruddock slots into the back row, as O'Mahony begins a three-match suspension.
For Ruddock - whose father Mike coached Wales to a Grand Slam in 2005 - it means a first Six Nations start more than a decade after his test debut at 19 years old, despite captaining his country on occasion.
The 30-year-old has been unlucky with injury and years of intense back row competition at club and country, but is playing some of best rugby of his career, winning Leinster's player of the month for three successive months to December.
Ireland: 1-Cian Healy, 2-Rob Herring, 3-Andrew Porter, 4-Tadhg Beirne, 5-Iain Henderson (captain), 6-Rhys Ruddock, 7-Josh van der Flier, 8-CJ Stander, 9-Jamison Gibson-Park, 10-Billy Burns, 11-James Lowe, 12-Robbie Henshaw, 13-Garry Ringrose, 14-Keith Earls, 15-Hugo Keenan
Reserves: Ronan Kelleher, Ed Byrne, Tadhg Furlong, Ultan Dillane, Will Connors, Craig Casey, Ross Byrne, Jordan Larmour