Lock James Ryan and centre Garry Ringrose have been ruled out of Ireland's final Six Nations match against England.
Ryan was taken off late in Ireland's win over Scotland for a head injury assessment, and will not have completed return-to-play protocols in time for Saturday's fixture in Dublin.
Ringrose, who has played every minute of Ireland's campaign so far, finished the game in Edinburgh but picked up an ankle injury that will be further assessed by Ireland and Leinster.
Flanker Peter O'Mahony is available for selection having missed the past three games through suspension.
The absence of the experienced Leinster duo is a considerable blow to head coach Andy Farrell, who credited Ryan for spearheading Ireland's impressive defensive line-out that was pivotal in their narrow victory over Scotland on Sunday.
It is the forward's second head injury of the tournament, having also missed the defeat by France.
The return of O'Mahony gives Farrell the option of moving Tadhg Beirne into the second row, but he may be loathe to take Beirne out of the back row where he has been so destructive in recent weeks.
Ringrose's absence means Robbie Henshaw will likely be partnered with either Bundee Aki, Chris Farrell and Stuart McCloskey in midfield.
Ireland are second in the Six Nations table but cannot catch leaders Wales while England are fourth.
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