Leon Brown, Rhys Patchell and Scott Williams have also been ruled out, Wales forwards coach Robin McBryde told a news conference on Monday.
But there was a boost for the team with five regulars being declared fit after being rated doubtful.
"It’s not as lengthy an injury list as last week," McBryde said as he confirmed the availability of Dan Biggar, Gareth Davies, Tomas Francis, Cory Hill and Ross Moriarty, who were all on the British and Irish Lions tour to New Zealand 18 months ago.
Davies had been a doubt after suffering a thigh muscle injury playing for the Scarlets this month.
Halfpenny’s participation – for the opening two rounds at least - was always in doubt after being told by a specialist he needed more time to get over the symptoms of concussion suffered against Australia in November.
(Reporting by Mark Gleeson, editing by Ed Osmond)
