Ronan Kelleher is set to miss Ireland's November internationals having been ruled out for up to eight weeks with a hamstring injury.
The hooker has not played for Ireland since a shoulder injury against France ended his 2022 Six Nations campaign.
Fly-half Harry Byrne (hamstring) and flanker Will Connors (bicep) are also out of next month's Tests.
Coach Andy Farrell's side host world champions South Africa on 5 November before playing Fiji and Australia.
Leinster's Kelleher made his return to competitive action in the United Rugby Championship last month after missing Ireland's victorious tour of New Zealand following a fresh shoulder injury sustained in the Champions Cup final.
Prior to his recent string of injuries Kelleher had established himself as a key contributor in a firing Irish pack, but his absence has opened the door for club-mate Dan Sheehan to present an equally compelling case for the starting jersey.
Back-row forward Connors has suffered another setback that is set to extend an already lengthy absence from the international frame.
He won the last of his nine caps against Scotland in March 2021, when a knee injury required surgery that saw him ruled out for the remainder of the season. Upon his return a fresh knee ligament injury in December would once more result in surgery that ended his 2021-22 campaign.
Ireland will also be without centre Bundee Aki for the visit of South Africa and Fiji, after the Connacht star received an eight-week ban following a red card for a dangerous clear-out against the Stormers in September.