Keith Earls will miss Ireland's entire RBS 6 Nations campaign with knee ligament damage that could keep him sidelined for two months.
The 26-year-old three-quarter's luckless injury run continues, after he limped out of Munster's 38-6 Heineken Cup victory over Edinburgh.
Earls signed a new two-year IRFU contract this week, rejecting strong overtures from Aviva Premiership and French Top 14 clubs.
Now he will sit out Ireland's Six Nations challenge as new head coach Joe Schmidt takes control of his first championship.
"Obviously we're really disappointed about Keith," said Schmidt.
"I think Keith is a super player and it's disappointing that we will be without him."
A new three-year IRFU contract for Jamie Heaslip was the antidote to Earls' disappointment, the 30-year-old rejecting the latest to spurn Toulon's advances.
Heaslip's signature ends worries any of Ireland's top stars will join Johnny Sexton in France next season.
Captain Paul O'Connell and Munster team-mate Earls, as well as Sean O'Brien and Ulster hooker Rory Best, have all now rejected moves to France.
Former Leinster boss Schmidt has admitted relief that Racing Metro fly-half Sexton will become Ireland's only frontline "exile", with Robin Copeland trading Cardiff for Munster next season.
Tommy Bowe will also miss a frantic opening where Ireland entertain Scotland and Wales in six days, the Ulster wing still recovering from groin trouble suffered in November.
Dave Kearney, Fergus McFadden, Luke Fitzgerald and Andrew Trimble will now compete to start on the wings, while Simon Zebo and Craig Gilroy prove fitness in Ireland Wolfhounds action at Gloucester on Saturday.
Knee problems kept Munster flyer Earls out of action for the entire autumn Test window.
New boss Schmidt is clearly keen to usher him into an Ireland jersey, but will not now get the chance during the upcoming championship, with Ireland starting their campaign against Scotland on February 2.
"I thought Dave Kearney did very well against the All Blacks," said Schmidt.
"Fergus McFadden made five clean line breaks when we had an ordinary performance against Australia.
"Luke Fitzgerald has been showing good form, but having Andrew Trimble back - I thought he was really good against Leicester and really good in the air.
"He brings a physical edge that maybe Tommy has got size wise, he's the other big guy.
"It's a luxury to get Craig Gilroy and Simon Zebo back. I still believe they may be a little bit short, not of quality, but of quality game time and so that's probably just why initially we weren't looking at those guys at the forefront.
"But it gives you a little bit of comfort if we do get injuries."
Heaslip's decision to commit his future to Leinster ends a period of speculation and uncertainty for the IRFU who had feared a number of stars joining Sexton in France.
Sexton has played significantly more club rugby with Racing Metro than he would in Ireland's provincial set-up, with Schmidt admitting Ireland had "lost control" of the player during the autumn Test series.
Ireland's careful player management has been central to their ability to retain this latest nucleus of talent then, especially given Wales' continued talent drain to the unrivalled salaries on offer in France's Top 14.
Penning a deal to run until 2017 is a clear indication Heaslip will now complete his career at his home province.
Relieved he can now concentrate on the upcoming RBS 6 Nations, "Leinster is where I wanted to continue playing and I am happy that the process is now at end," said Heaslip.
"I am looking forward to playing my role in driving success for both Leinster and Ireland."
British Lion Heaslip made his Leinster debut in 2005 and has since amassed 176 appearances, scoring 34 tries.
The 60-cap loose-forward first featured for Ireland against the Pacific Islanders in November 2006, and has claimed a Grand Slam and three Heineken Cup titles in his career.