Ireland head coach Joe Schmidt has rested experienced duo Rory Best and Johnny Sexton for the autumn international opener against Italy to be played in Chicago on 3rd November.
The duo will be joined by the likes of Peter O'Mahony, Rob Kearney, Iain Henderson, Rob Herring and Stuart McCloskey and Keith Earls to miss out on the Saturday's encounter.
Sexton's absence means uncapped fly-half Ross Byrne will have to compete with Joey Carbery for the number 10 spot.
With Conor Murray sidelined with neck injury John Cooney and Luke McGrath will look to fight it out for the scrum-half.
Ulster's Will Addison will be hoping to win his first Test cap while Jacob Stockdale, Jordan Larmour, Andrew Conway and Darren Sweetnam are in contention for the back three.
The last time Ireland played in Chicago was in November 2016 when they defeated New Zealand for the first time.
Following the game against Italy, Ireland will take on Argentina, New Zealand and the United States of America on 10th, 17th and 24th November respectively.
Ireland's 26-man squad:
Forwards: Finlay Bealham, Tadhg Beirne, Jack Conan, Sean Cronin, Tadhg Furlong, Dave Kilcoyne, Jack McGrath, Jordi Murphy, Andrew Porter, Quinn Roux, Rhys Ruddock, James Ryan, Niall Scannell, Devin Toner, Josh van der Flier
Backs: Will Addison, Bundee Aki, Ross Byrne, Joey Carbery, Andrew Conway, John Cooney, Jordan Larmour, Luke McGrath, Garry Ringrose, Jacob Stockdale, Darren Sweetnam