Ireland head coach Joe Schmidt has included Connacht's newly Irish-qualified centre Bundee Aki, while dropping Simon Zebo for autumn internationals against Argentina, Fiji and South Africa.
Zebo announced his end-of-the-season departure from Munster this week and has seen his place in the side go while Aki has been brought in after he qualified on residency.
Garry Ringrose (shoulder), Jared Payne (migraines), Jamie Heaslip (back) and Josh van der Flier (syndesmosis) have all been ruled out with injury while Rob Kearney is set to return after a spell on the sidelines due to a hamstring injury.
Joining Aki in the backs are three other uncapped players in Munster duo Darren Sweetnam and Chris Farrell and Leinster's Adam Byrne while Ulster's Tommy Bowe and Andrew Trimble miss out.
"In what we anticipate will be an incredibly physical Guinness Series plenty will be demanded of the squad," Schmidt said. "We have retained a core of experienced players but have also included a number of promising players that we hope will acquit themselves well."
Ireland squad
Forwards: Best, Conan, Dillane, Furlong, Healy, Henderson, Herring, Kilcoyne, Leavy, McGrath, O'Brien, O'Donnell, O'Mahony, Porter, Ruddock, Ja. Ryan, Jo. Ryan, Stander, Toner, Tracy, Treadwell. BACKS
Backs: Aki, Byrne, Joey Carbery, Conway, Earls, Farrell, Henshaw, D Kearney, R Kearney, Keatley, Marmion, McCloskey, McGrath, Murray, Sexton, Stockdale, Sweetnam.