Dublin - South Africa-born flank CJ Stander will make his Ireland debut against Wales on Sunday, but coach Joe Schmidt was left counting a mounting injury toll with star flank Sean O'Brien and fullback Rob Kearney ruled out.
Only new skipper and hooker Rory Best, No 8 Jamie Heaslip and lock Devin Toner have retained their starting berths from Ireland's 43-20 Rugby World Cup quarter-final defeat to Argentina.
Munster back-rower Stander will start at blindside at Dublin's Aviva Stadium, the 23-year-old having completed his Ireland qualification on residency grounds.
Leinster duo O'Brien and Kearney have both failed to beat hamstring trouble in time to face Wales, so Tommy O'Donnell slots in at openside flank and Simon Zebo at fullback.
O'Brien and Kearney sat out training on Friday, but Ireland will hope to have two of their most experienced men fit in time for the second-round clash against France in Paris.
Flank O'Donnell dislocated his hip in Ireland's 35-21 warm-up victory over Wales in Cardiff in August.
The 28-year-old has hit back to fitness and form with Munster however, and will be a popular selection among Ireland's squad given his bad injury luck in missing the World Cup.
Even leaving aside former captain Paul O'Connell, now retired from Test rugby, Ireland are still shorn of six regulars in their pack this weekend.
Props Cian Healy and Mike Ross, lock Iain Henderson, and flanks Peter O'Mahony and Chris Henry join O'Brien on the treatment table.
Stander's debut has been accelerated due to O'Mahony's absence, but the former Springboks Under-20s star has excelled in his three years with Munster.
The Thomond Park province's European Champions Cup captain would have risen to Test prominence earlier had he not had to bide his time for residency qualification.
Kearney's absence in the backline hands Munster's livewire attacking talent Zebo a chance to impress, with Schmidt refusing to stray from a tried and tested midfield line-up.
Schmidt has restored his preferred midfield partnership of Robbie Henshaw and Jared Payne, refusing the temptation to pitch bullish Ulster centre Stuart McCloskey in for a Test debut.
With Tommy Bowe and Luke Fitzgerald both long-term absentees, Keith Earls partners Andrew Trimble on the wings.
Ireland team announced for Sunday's Six Nations game against Wales at Dublin's Aviva Stadium (17:00 kick-off SA time):
15 Simon Zebo, 14 Andrew Trimble, 13 Jared Payne, 12 Robbie Henshaw, 11 Keith Earls, 10 Jonathan Sexton, 9 Connor Murray, 8 Jamie Heaslip, 7 Tommy O'Donnell, 6 CJ Stander, 5 Devin Toner, 4 Mike McCarthy, 3 Jack McGrath, 2 Rory Best (captain), 1 Nathan White
Substitutes: 16 Sean Cronin, 17 James Cronin, 18 Tadhg Furlong, 19 Donnacha Ryan, 20 Rhys Ruddock, 21 Kieran Marmion, 22 Ian Madigan, 23 Dave Kearney
15 Gareth Anscombe, 14 George North, 13 Jonathan Davies, 12 Jamie Roberts, 11 Tom James, 10 Dan Biggar, 9 Gareth Davies, 8 Taulupe Faletau, 7 Justin Tipuric, 6 Sam Warburton (captain), 5 Alun Wyn Jones, 4 Luke Charteris, 3 Samson Lee, 2 Scott Baldwin, 1 Rob Evans
Substitutes: 16 Ken Owens, 17 Gethin Jenkins, 18 Tomas Francis, 19 Bradley Davies, 20 Dan Lydiate, 21 Lloyd Williams, 22 Rhys Priestland, 23 Alex Cuthbert