Eddie O’Sullivan has been forced into making a third change to his 22-strong squad for Sunday's Six Nations opener against Wales with the loss of centre Shane Horgan with a rib injury.
Keith Wood and Lions team-mate Malcolm O'Kelly had withdrawn earlier in the day after failing to shake off injuries.
And O'Sullivan, preparing for his first game in charge of the national side, has also given up hope of having Horgan fit.
The Leinster centre went off early in the second half of his side's 29-18 Heineken Cup quarter-final defeat at Leicester yesterday after taking a knock to his ribs.
Horgan's replacement is Lions centre Rob Henderson, who originally had to be content with a place in the Ireland A team after missing most of the season with a knee injury.
He will be vying with Kevin Maggs for a place alongside Brian O'Driscoll when the selectors name the starting line-up on Wednesday.
Wood, the International Rugby Board’s international player of the year, conceded defeat to a calf injury after failing to turn out for Harlequins in their Zurich Premiership match at the weekend, while O'Kelly missed Leinster's cup-tie with a fractured cheekbone.
Munster hooker Frank Sheahan will make only his second start as Wood's replacement, while Leinster's Shane Byrne is promoted from the A squad to the bench.
Paul O'Connell, man of the match in Munster's 16-14 Heineken Cup quarter-final win at Stade de France on Saturday, comes in for his first cap in place of O'Kelly.