Brian O'Driscoll and Sean O'Brien are the latest admissions to the treatment room and the Leinster duo have been ruled out of Saturday's clash with England at the Aviva Stadium.
O'Driscoll suffered a knock to his shoulder in last weekend's 26-22 defeat by France and has been omitted as a precautionary measure.
At this stage there is no doubt over his participation in the World Cup opener against the United States on September 11, but his lack of game time is a concern.
Having overcome a different neck/shoulder injury to make his first appearance of the summer last Saturday, he will now head to New Zealand with just 80 minutes of rugby in the bank.
"Brian's had injuries like this before," said coach Declan Kidney, who has picked Keith Earls at outside centre.
"There's a World Cup coming after this and it's more important that he's ready for that than this game.
"He's running around outside, but it was prudent not to put him into a contact situation on Saturday.
"He has made good progress, especially over the last 24 hours.
"Sometimes you just need to rest up and get it out of the system."
A further source of anxiety is a knee injury incurred by European player of the year O'Brien in the second of the two defeats by France.
The bulldozing O'Brien - undoubtedly Ireland's best performer since January - is likely to face the USA, but Kidney was far from emphatic on his prospects.
"Sean has a bit of a tear on one of the ligaments, but he has been training already this morning," said Kidney.
"It's not like he's laid up in bed or anything like that. It just goes with the territory in sport, unfortunately.
"He's not available for England and then we don't have another game for two weeks.
"We are hopeful he will be available for the America match."
Factor in another week on the sidelines for Rob Kearney because of his groin injury - Geordan Murphy slots in at full-back - and the squad's fitness profile is clearly a concern.
The tension will have eased on Saturday evening, however, if Stephen Ferris, David Wallace and Tommy Bowe come through unscathed.
Ferris, the highly destructive Lions back row, has been dogged by a knee problem since January but negotiated his final-quarter cameo against France unscathed.
O'Brien's injury gives Ferris an opportunity to prove his fitness, while Wallace and Bowe will be making their first appearances of the summer after recovering from respective hamstring and foot injuries.
Further encouragement is supplied by the selection of Jerry Flannery, who has been dogged by calf problems, at hooker for his first Ireland start since last year's RBS 6 Nations.
The focus on injuries has gone some way to deflecting attention from the importance of Saturday's Test against England.
A run of three successive defeats has made victory imperative for Ireland if they are to depart for New Zealand with any sort of momentum.
"I'm disappointed we've lost the last three matches but I know we can get ourselves right," said Kidney.
"We decided to have four warm-up internationals because in the past it's taken us a while to get into our stride.
"I believe we'll get into our stride now, but there are a few bits of the jigsaw that must come together and that's what we're trying to achieve."
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