Ulster skipper Iain Henderson will miss the side's European opener against Toulouse on Friday night and head coach Dan McFarland has said there will be "no quick turnaround" from the knee injury the lock sustained on international duty.
The 28-year-old was replaced in the first-half of Ireland's win over Scotland and Ulster, who are already without Henderson's suspended second-row colleague Kieran Treadwell, now find themselves stretched in the lock department ahead of a key run.
The timing of the injury to the former British and Irish Lion could hardly be worse for the province given the stretch of matches to come, with four European games and three interpros between now and the end of January.
"It's a big loss for us," McFarland admitted. "Iain is a talismanic figure for us, he's our club captain.
"He's a big game player for us and he's played really big games for us in the recent past and throughout his career.
"Having said that, Al (O'Connor) and Sam Carter have been doing a tremendous job in the engine room and they'll continue with that."
When pushed for a time-frame on the injury, McFarland sounded less optimistic.
"Not yet," he said of a return date ahead of a planned visit to a knee specialist this week.
"We'll hang onto that info until we have a specific timeframe but it's not going to be a quick turnaround, I can tell you that."
Henderson is not the only front-line absentee for the weekend.
With Luke Marshall, Will Addison and Robert Baloucoune all already out, there was a further piece of bad news from Ireland camp with Billy Burns having not recovered from the groin injury he picked up against Georgia two weeks ago.
"To lose your captain and you lose your ten as well," McFarland added.
"That's a difficult one but again we've played a number of games over the past while and played pretty well, albeit not at the same level we're about to face.
"The guys that have played while Billy has been with Ireland have done a great job and we'll be happy to trust in them."