Ireland captain Paul O'Connell and scrum-half Conor Murray have been ruled out of the rest of the Six Nations.
Lock O'Connell suffered medial ligament damage after twisting his left knee in Sunday's 17-17 draw with France and will be sidelined for up to six weeks.
Murray will be out for at least three weeks after being stretchered off in Paris with bruising to a knee joint.
Connacht forward Mike McCarthy and Munster scrum-half Tomas O'Leary have been added to the Irish squad as cover.
Ulster hooker Rory Best is being tipped to be installed in the captaincy when the Ireland team for Saturday's game against Scotland is announced on Wednesday.
While McCarthy and O'Leary have been drafted into the Irish squad, Donnacha Ryan and Eoin Reddan are likely to replace O'Connell and Murray in the starting line-up.
A scan showed that O'Connell injured his medial collateral ligament and he will have a three to six weeks recovery period.
Murray sustained his injury when he fell awkwardly on his right knee, and he was replaced after 59 minutes.
The Munster pair will miss the Saturday's encounter with Scotland at the Aviva Stadium and the final Six Nations game away to England a week later.
O'Connell is also a doubt for Munster's Heineken Cup quarter-final against Ulster on 8 April although Murray should be fit for the Thomond Park clash.
Losing both players, but especially talismanic 85-cap veteran O'Connell, is the latest setback to an Irish campaign haunted by misfortune.
On the opening weekend Wales triumphed at the Aviva Stadium with a controvesial last-minute penalty.
Six days later their trip to Paris was rendered a waste of time when the frozen Stade de France pitch was deemed unplayable - 10 minutes before kick-off.
Forwards coach Gert Smal was ruled out of the remainder of the Six Nations by an eye condition on the eve of the 42-10 win over Italy and the Irish then squandered a 17-6 half-time lead as they drew against France on Sunday.