Garry Ringrose and Devin Toner have been ruled out of Ireland's Six Nations clash with Scotland on Saturday.
Centre Ringrose suffered a hamstring injury when the defending champions started the defence of their title with a 32-20 home defeat to England last weekend.
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Toner was withdrawn in the second half at the Aviva Stadium due to an ankle injury and the towering lock will not feature at Murrayfield.
There is better news of wing Keith Earls, who came off at half-time against Eddie Jones's men in Dublin with a hip injury but was able to train on Monday.
Back-row CJ Stander was on Monday ruled out of the matches against Scotland and Italy with a facial injury.
