Ireland will begin their World Cup without Joey Carbery as well as Rob Kearney, Keith Earls and Robbie Henshaw.
Garry Ringrose has won the battle to partner Bundee Aki at centre against Scotland in Yokohama on Sunday, with Joe Schmidt handing him a start at no 13, ahead of Chris Farrell.
Jordan Larmour has been named at full-back in place of Kearney, while Andrew Conway comes in for Earls.
Carbery, who hasn't played since ankle surgery after the first World Cup warm-up against Italy six weeks ago, is not being risked off the bench against the Scots.
The 23-year-old's ability to cover a number of backline positions will be missed. He is expected to feature against hosts Japan next week.
Connacht's Jack Carty, who has seven Test appearances behind him, will start instead as back-up to Johnny Sexton as Joe Schmidt has been forced to rearrange his backline for the clash with Ireland's Six Nations rivals.
Schmidt will have confidence in 27-year-old Carty, who was impressive after replacing Sexton after 23 minutes of Ireland's victory over the Scots in the Six Nations last February.
As was rumoured in midweek, Kearney isn't fit enough to start after suffering tightness in his calf in training.
Fellow veteran Earls returned to full training on Friday after a knee problem that he suffered in the final warm-up against Wales.
But that was too late to convince Schmidt that he could start.
Apparently both Kearney and Earls were close to full fitness and, had it been a quarter-final rather than a first pool game, they would have been risked.
Instead, Jordan Larmour will take Kearney's no 15 jersey, while Conway lines out on the wing.
The pack is along expected lines with Iain Henderson and James Ryan partnering up in the second row, and Tadhg Beirne providing cover off the bench.
Despite making a push to wear the no 8 jersey, Jack Conan is among the replacements with CJ Stander retaining his spot.
Skipper Rory Best wins his 121st Ireland cap at hooker, while alongside him in the front row Cian Healy makes his 92nd appearance in the green shirt.
IRELAND: J Larmour, A Conway, G Ringrose, B Aki, J Stockdale, J Sexton, C Murray; C Healy, R Best, T Furlong, J Ryan, I Henderson, P O'Mahony, J van der Flier, CJ Stander.
Replacements: N Scannell, D Kilcoyne, A Porter, T Beirne, J Conan, L McGrath, J Carty, C Farrell.
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