Ireland forwards Paul O'Connell and Stephen Ferris will not be fit in time for the final autumn international against Argentina on 24 November.
The Lions duo missed the 16-12 defeat by South Africa in Dublin and had already been ruled out of this Saturday's uncapped meeting with Fiji.
O'Connell was sidelined with a back problem while Ferris sustained an ankle injury while playing for Ulster.
On Monday, the IRFU said both would miss all the autumn internationals.
The Lions forwards' absence means Ireland will be without six key personnel against the Pumas, with Brian O'Driscoll, Rory Best, Rob Kearney and Sean O'Brien completing the list.
Meanwhile, Eoin Reddan is a doubt for the non-Test clash with Fiji at Thomond Park.
The Leinster scrum-half was to have a scan on the ankle injury picked up in the South Africa match.
However, forwards Donnacha Ryan and Cian Healy have been given the all clear to resume training after picking up slight knocks.