Ken Owens will miss the whole of Wales' Autumn Nations Series with a back injury, the Welsh Rugby Union announced Monday.
The experienced hooker was absent from Saturday's 23-18 loss to world champions South Africa and has now pulled out of coach Wayne Pivac's squad.
The British and Irish Lions forward had been named in Wales' initial line-up for a 54-16 defeat by New Zealand in October, but withdrew shortly after the team to play the All Blacks in Cardiff had been announced.
And now the 34-year-old will miss this month's Principality Stadium encounters with both Fiji and Australia as well.
"Ken Owens has been released from the national squad due to a back injury which will prevent him from taking any part in the Autumn Nations Series," the WRU statement said.
Ryan Elias was the starting hooker in the Wales side that ran the Springboks close, with Ulster's Bradley Roberts making his debut off the bench late on.
Meanwhile, the spectator who invaded the pitch during the South Africa match has been given a lifetime ban from the Principality Stadium.
Wales full-back Liam Williams was on the attack near the Springboks' line in the 65th minute when he had to leap over a spectator who had evaded the stewards before the culprit was detained by stadium staff.
"The WRU, Principality Stadium and South Wales Police condemns any behaviour of this kind and the individual will be issued with a lifetime ban from buying any tickets from the WRU for rugby events held at the Principality Stadium in future," said stadium manager Mark Williams.
"We were deeply disappointed to discover the individual is a register player and member of a rugby club; the WRU are currently investigating this as a code of conduct breach."
Six Nations champions Wales face Fiji on Sunday before rounding off the international year against the Wallabies on November 20.