Peter O'Mahony is out of Ireland's World Cup campaign due to a serious injury, while Sean O'Brien could miss the quarter-final with Argentina over disciplinary wrangles.
The staggering collateral damage from Sunday's superlative 24-9 victory over France could see as many as three fresh faces join Ireland's World Cup squad as injury replacements.
O'Mahony flew home to Cork today after suffering knee ligament damage, to be replaced by Leinster's Rhys Ruddock.
Talisman Paul O'Connell is awaiting the formalities of confirmation that both his tournament and Test career are over.
Ireland captain O'Connell spent Sunday night in hospital with a "significant hamstring injury", and flanker O'Brien was cited for appearing to punch France lock Pascal Pape.
"Paul O'Connell appears to have suffered a significant hamstring injury and was hospitalised overnight. He's having scans later today to clarify the extent of the injury," team manager Mick Kearney said today.
"Peter O'Mahony has suffered a knee ligament injury and is returning to Dublin today for specialist opinion and will take no further part in the tournament.
"Johnny Sexton suffered a groin injury, initial clinical assessment is encouraging and we await scanning later today.
"After an incredibly physical encounter a host of players are reporting bumps and soreness and will have to be managed, but nothing more serious than that.
"As soon as we have more clarity on the injury front we will be in a position to make decisions on replacement players.
"At the moment, definitively, only Peter O'Mahony has been ruled out. Paul was in hospital overnight and he was obviously very sore.
"In relation to Jared Payne's replacement, that's similar too. I'd be pretty sure that a decision would be made later today.
"The coaches did meet this morning and discuss a number of different options."
Flanker O'Brien's citing was confirmed by World Rugby on Monday evening, with a disciplinary hearing set for Tuesday lunchtime in London.
Independent judicial officer Terry Willis will hear O'Brien's case, with Ireland boss Joe Schmidt revealing hopes on Sunday that the combative Leinster flanker could avoid sanction.
France coach Philippe Saint-Andre has branded O'Brien's clash with Pape an "assault", but Schmidt claimed his back-rower had connected with an "open hand".
Ireland's chances of beating the ebullient Pumas would be sorely tested should Schmidt's men be forced to cope without O'Brien, as well as O'Mahony and O'Connell.
Ireland are yet to name a replacement for centre Jared Payne, but started their cavalry call by adding 24-year-old Ruddock to their ranks to offset the loss of O'Mahony.
Andrew Trimble is in the frame to slot in for Payne, ruled out with a fractured foot, while Dan Tuohy could be lined up to slot in for O'Connell.
O'Connell's Test career appears to be at an end after 108 caps.
The 35-year-old was due to retire from the Test arena at the end of the competition, but the severity of his injury will surely accelerate that process.
The Toulon-bound second row beat the Millennium Stadium turf in anguish and anger after suffering his injury, before being carried off on a stretcher at half-time during Sunday's France clash.
Full-back Rob Kearney accepted O'Connell's World Cup was effectively at an end, admitting Ireland will suffer in his absence.
"There's not much I can say here now in the next 30 seconds that can give testament to his contribution to Irish rugby and this World Cup," Kearney said.
"Of course if he is ruled out it's going to be a monumental loss to us.
"The form he's in is superb. He looks as though he's really enjoying his rugby too, and you always say when guys look like they're really enjoying what they're doing that's generally when they get the best out of themselves.
"If it is the case it would be massively gutting and disappointing, and we'd have lost one of our key players."
Kearney hailed O'Connell for "beaming ear to ear" at Ireland's victory, despite fearing the worst on a personal front.
"I suppose the fact that he's been around more than any of us at World Cups, it is difficult for him," Kearney said, accepting O'Connell's fate.
"We felt awful for him, but I think it was great to see the sheer delight on his face after the game in terms of what we'd achieved as opposed to feeling sorry for himself."