Leigh Halfpenny has been ruled out of Wales' Under Armour Series finale against South Africa in Cardiff on Saturday.
The goalkicking full-back suffered concussion following a challenge by Australia centre Samu Kerevi when Wales beat the Wallabies 10 days ago.
Kerevi escaped sanction following the incident, but Wales have now lost 80 times-capped Halfpenny for the Springboks fixture.
"Leigh is out," Wales assistant coach Rob Howley told reporters at Wales' training base on Tuesday.
"He did some training on Saturday morning, and he was still feeling a little bit light-headed.
"It is just a commonsense approach, really. A player's welfare comes first. He unfortunately misses out this weekend."
Wales have options in the number 15 shirt, with Liam Williams, who started on the wing and scored two tries against Tonga last weekend, one candidate.
And fly-half Gareth Anscombe could be another contender as Wales look to complete a first clean sweep of autumn Test victories.
They are also chasing a ninth successive win against all opponents, which would equal their longest unbeaten run since 1999.
Wales head coach Warren Gatland is due to announce his startling line-up on Thursday.
Halfpenny is Wales' first-choice goalkicker and has amassed more than 700 points for his country, but Wales also have strong options in that area with the likes of Anscombe, Dan Biggar and Rhys Patchell.
Howley, meanwhile, confirmed that wing George North is back in training after suffering a dead leg during the Wallabies clash.
"I'm glad to say George North is back in full training," Howley added. "He trained this morning and is available for selection."