Peter O'Mahony will also miss the Murrayfield clash
Ireland have been dealt a major blow ahead of the opening game of the Six Nations with the news that Johnny Sexton is to miss the Scotland game.
Sexton has not played since Leinster's Champions Cup draw with Castres earlier this month, when he injured his calf. The injury was aggravated on Monday, and he will not be fit in time to face Scotland.
"He ran yesterday afternoon and felt a little bit of tightness in his calf," Ireland forwards coach Simon Easterby confirmed on Tuesday afternooon. "We believe it right not to push him through the week and risk potential further damage.
"He's obviously had a number of lower limb injuries, one being a hamstring injury that we managed along with Leinster through the pre-Christmas period after the Autumn... He picked up a calf bump in the week of the Castres game."
Paddy Jackson is expected to step in, in Sexton's absence, with Ian Keatley the most likely to take his spot on the bench.
Easterby also confirmed the Peter O'Mahony is out of the game in Edinburgh. The Munster flanker has suffered a hamstring injury. Ulster winger Andrew Trimble is unlikely to feature, but has yet to be ruled out, after suffering a groin strain.
Jackson led Ireland in the three-test series against South Africa during the summer, and has been the heir to Sexton's throne in recent years. He featured in all three of Ireland's Autumn internationals, and started in the wins over Canada and Australia.
No further injury news was released from the Ireland squad in Carton House, with more expected on Wednesday afternoon.