Wales captain Sam Warburton has been joined by replacement scrum-half Lloyd Williams in missing Saturday's RBS Six Nations game against Italy in Cardiff.
Cardiff Blue Williams has a thigh strain and his bench place has been taken by uncapped Osprey Rhys Webb.
Openside Warburton's knee injury means Justin Tipuric starts at seven, while centre Jamie Roberts does play despite his own knee problems.
Prop Gethin Jenkins captains Wales even though ex-skipper Matthew Rees returns.
Webb, 23, has represented Wales Under-18, Under-19 Under-20 and Wales Sevens after playing his formative rugby at Bridgend Athletic RFC.
Rees takes over from fellow Scarlet Ken Owens at hooker while Lock Luke Charteris is named on the bench after returning from injury.
The 28-year-old had been sidelined with a long-term wrist injury since the end of the 2011 World Cup.
But Charteris returned to action for Newport Gwent Dragons on Saturday in their Pro12 24-14 defeat at home to Munster.
Centre Scott Williams, who scored the winning try against England last time out as Wales sealed the Triple Crown, is again among the replacements.
His Scarlets team-mate Owens also has to be content with a place on the bench thanks to the return of British and Irish Lion Rees after a calf injury, with Richard Hibbard the hooker to miss out completely.
Rees, who last played on 14 January for the Scarlets, packs down between Adam Jones and Jenkins to reform the Lions front-row that took on South Africa in 2009.
"Due to injuries to all three players at one time or another we have not been able to field this 2009 Lions front row too often," said Wales head coach Warren Gatland.
"So, although we are more than happy with the job Ken has done for us, we are giving Matthew the opportunity to make his contribution as the competition reaches its climax.
"We are back at the Millennium Stadium in front of our home fans and we need to refocus sharply, after our Triple Crown triumph at Twickenham, if we are to give ourselves the best chance of being in contention for the Championship going into that final weekend against France.
"Italy will be hoping to find us complacent and with one eye on the French game, but nothing less than victory on Saturday will be accepted by this Wales team or satisfy the nation behind us.
"All of that leaves the players themselves brimming with ruthless intent."
Utility back James Hook has recovered from his bout of chicken pox, playing in Perpignan's 22-17 defeat by Agen at the weekend, and is also held in reserve, meaning fly-half Stephen Jones drops out of the match 22 completely.
Victory at the Millennium Stadium against the Azzurri will keep Gatland's side on course for a third Grand Slam in eight years, with France the final hurdle to face in Cardiff on 17 March.
Wales are unbeaten against Italy at the Millennium Stadium and only Gatland's men can now win a Grand Slam this year by holding them to a 17-17 draw in Paris.
WALES: Leigh Halfpenny (Blues); Alex Cuthbert (Blues), Jonathan Davies (Scarlets), Jamie Roberts (Blues), George North (Scarlets); Rhys Priestland (Scarlets), Michael Phillips (Bayonne); Gethin Jenkins (Blues, capt), Matthew Rees (Scarlets), Adam Jones (Ospreys), Alun Wyn Jones (Ospreys), Ian Evans (Ospreys), Dan Lydiate (Dragons), Justin Tipuric (Ospreys), Toby Faletau (Dragons).
REPLACEMENTS: Ken Owens (Scarlets), Paul James (Ospreys), Luke Charteris (Dragons), Ryan Jones (Ospreys), Rhys Webb (Ospreys), James Hook (Perpignan), Scott Williams (Scarlets).
Backs: Mike Phillips (Bayonne), Lloyd Williams (Cardiff Blues), Rhys Webb (Ospreys), Rhys Priestland (Scarlets), James Hook (Perpignan), Stephen Jones (Scarlets), Jamie Roberts (Cardiff Blues), Jonathan Davies (Scarlets), Scott Williams (Scarlets), Gavin Henson (Cardiff Blues), Ashley Beck (Ospreys), George North (Scarlets), Leigh Halfpenny (Cardiff Blues), Alex Cuthbert (Cardiff Blues), Harry Robinson (Cardiff Blues), Liam Williams (Scarlets), Lee Byrne (Clermont Auvergne)
Forwards: Craig Mitchell (Exeter Chiefs), Adam Jones (Ospreys), Ryan Bevington (Ospreys), Gethin Jenkins (Cardiff Blues), Paul James (Ospreys), Rhys Gill (Saracens), Rhodri Jones (Scarlets), Matthew Rees (Scarlets), Huw Bennett (Ospreys), Ken Owens (Scarlets), Richard Hibbard (Ospreys), Alun Wyn Jones (Ospreys), Ian Evans (Ospreys), Lou Reed (Scarlets), Luke Charteris (Newport Gwent Dragons), Ryan Jones (Ospreys), Dan Lydiate (Newport Gwent Dragons), Sam Warburton (capt, Cardiff Blues), Justin Tipuric (Ospreys), Toby Faletau (Newport Gwent Dragons), Andy Powell (Sale Sharks), Aaron Shingler (Scarlets).