Ireland forwards Caelan Doris and Quinn Roux have been ruled out of Sunday's Six Nations opener against Wales.
Back row Doris has returned to Leinster because of concussion symptoms while Connacht lock Roux has a neck injury.
Munster back row Gavin Coombes and Leinster lock Ryan Baird have been added to the Ireland training squad for the game in Cardiff.
Ireland report no other injury worries with captain Johnny Sexton set to train with the squad this week.
Iain Henderson also looks in contention to feature having not played since sustaining a knee injury in Ireland's Autumn Nations Cup game against Scotland in early December.
Sexton picked up what was described as a "minor muscle injury" in Leinster's win over Munster 10 days ago but said last week that he expected to be fit for the Cardiff game.
An IRFU statement said Doris had "flagged some symptoms that could be associated with concussion".
"He has returned to Leinster to allow his symptoms to be appropriately assessed and investigated.
"Quinn has a neck complaint that has not settled so he has returned to Connacht."
Doris, 22, has won seven Ireland caps with South Africa-born Roux, 30, making 16 appearances for his adopted country.
The Leinster back row was arguably Ireland's standout performer during the inaugural Autumn Nations Cup campaign while Roux would also have been in contention to play in Cardiff.