Declan Kidney has named his starting XV to face France, but has been forced to leave the out-half position vacant as Paddy Jackson battles a hamstring injury.
Jonathan Sexton was deemed unfit and has been withdrawn from the squad for Saturday's clash at Aviva Stadium.
Craig Gilroy has also been ruled out with a groin injury and is replaced on the wing by Fergus McFadden.
Cian Healy returns in the front row after suspension in place of Tom Court and Mike McCarthy regains his place in the second row at the expense of Donncha O’Callaghan.
There are two gaps in the replacements with no out-half named, and Stephen Archer or Michael Bent will be chosen as replacement prop with Declan Fitzpatrick ruled out through injury.
"Paddy's chances of pulling through are very good and he should be good to train on Thursday," Kidney said.
"We'll make the choice between Paddy and Ian then. I was told just a moment ago that it will be better to give Jonathan Sexton another week to recover.
"Jonny ran at top speed this morning. It would be easy to put him in against France, but it's better that he builds up his strength for another week."
Ireland record's against pre-tournament favourites France is dismal having registered a solitary victory in their last 13 meetings - the Grand Slam-winning year of 2009 - in a sequence dating back to 2003.
But the form of the winless French has been even more startling and they are seeking to avoid a first championship whitewash since 1957 and first wooden spoon since 1999.
Ireland XV to play France: Kearney, McFadden, O’Driscoll, Marshall, Earls, AN Other, Murray, Healy, Best, Ross, McCarthy, Ryan, O’Mahony, O’Brien, Heaslip (Capt).
Replacements: Cronin, Kilcoyne, AN Other, O’Callaghan, Henderson, Reddan, AN Other, Fitzgerald.