Robbie Henshaw will miss Ireland's Argentina clash with a suspected hamstring injury, while Leinster wing Adam Byrne will make his Test debut in Dublin on Saturday.
British and Irish Lions centre Henshaw missed training on Thursday, leaving him unable to contest selection to face the Pumas.
Munster's Chris Farrell will start in the centres, winning his second cap, as Ireland bid to offset the loss of one of their top stars in Henshaw.
Head coach Joe Schmidt has recalled a raft of frontline stars for the Argentina game following last weekend's edgy 23-20 win over Fiji which was achieved by an experimental line-up.
James Ryan will partner Iain Henderson in a powerful second row combination, with Bundee Aki in line for his second Test start at inside centre.
Leinster flyer Byrne was handed his provincial debut as a 19-year-old by Schmidt, but has since had to endure two broken legs amid staccato progress to his promising career.
But now the 23-year-old has been handed the chance to step up to the next level, and boss Schmidt will be hoping his top-line pace can add extra zip to Ireland's backline.
— Irish Rugby (@IrishRugby) November 23, 2017
Schmidt admitted Henshaw has picked up a hamstring issue and insisted Ireland were not ready to risk one of their top assets.
The former Leinster coach also backed Munster man Farrell to cope when slotting back into the starting line-up.
"He's got a slight hamstring strain," said Schmidt, of Henshaw.
"I think at a push he could potentially have been involved.
"But it should see him fine for what's coming up (with Leinster), he's got a busy period coming up.
"This window was a chance to see how guys do in pressure situations.
"Chris (Farrell) acquitted himself pretty well last week, got better as the game went on, and it's another opportunity for him."
Ireland team to play Argentina
Forwards: 1 Cian Healy (Leinster), 2 Rory Best (CAPTAIN, Ulster), 3 Tadhg Furlong (Leinster), 4 James Ryan (Leinster), 5 Iain Henderson (Ulster), 6 Peter O'Mahony (Munster), 7 Sean O'Brien (Leinster), 8 CJ Stander (Munster)
Backs: 9 Conor Murray (Munster), 10 Johnny Sexton (Leinster), 11 Jacob Stockdale (Ulster), 12 Bundee Aki (Connacht), 13 Chris Farrell (Munster), 14 Adam Byrne (Leinster)*, 15 Rob Kearney (Leinster)
Replacements: 16 James Tracy (Leinster), 17 Dave Kilcoyne (Munster), 18 John Ryan (Munster), 19 Devin Toner (Leinster), 20 Rhys Ruddock (Leinster), 21 Luke McGrath (Leinster), 22 Ian Keatley (Munster), 23 Andrew Conway (Munster)
* Denotes uncapped player