Ireland hooker Ronan Kelleher is expected to be sidelined for the autumn series opener against New Zealand in Dublin on 8 November.
His club side Leinster said on Monday the front row “will be unavailable for four to six weeks after undergoing a procedure on an ankle injury”.
The 26-year-old’s injury setback also makes him a doubt for the Aviva Stadium matches against Argentina a week later and then Fiji on 23 November.
Ireland conclude the series by taking on Australia on 30 November.
First-choice hooker Dan Sheehan is also out with a long-term knee injury while Ulster pair Rob Herring and Tom Stewart have not played yet this season.
There’s some better news for Leinster and Ireland with Robbie Henshaw returning for Saturday’s United Rugby Championship derby against Connacht in Galway.
A minor injury ruled the centre out of last weekend’s 26-12 victory over Munster at Croke Park.
Leinster will be without Jack Conan and Joe McCarthy for the trip to Galway because of hamstring injuries, while Lee Barron, Ryan Baird and Jordan Larmour are doubts.