Wales have suffered a late blow ahead of Saturday's clash with South Africa after the luckless Eli Walker was ruled out through injury.
The Ospreys winger picked up a hamstring problem during training on Thursday, Wales team management have confirmed.
The 21-year-old was set to make his international debut against the Springboks at the Millennium Stadium, but his place on the wing has now been taken by Scarlets' Liam Williams with Ospreys' Ashley Beck stepping up to the bench.
Walker has suffered a number of injury setbacks over the last year, and it remains to be seen if his hamstring problem will rule him out of the upcoming fixtures against Argentina, Tonga and Australia.
He was named in Wales' initial Six Nations squad at the start of the year before being forced to undergo surgery on a back ailment which ended his season.
"We are fearing the worst, but I am sure the scan results will point us in the right direction," Wales assistant coach Rob Howley said.
"Eli pulled up this morning with a hamstring strain. We are not too sure whether it is a grade one or grade two.
"We will await the results of the scans and the likelihood that he might not be available for the whole of the autumn series, which is a blow to us."
Prolific try-scorer Alex Cuthbert is also sidelined with an ankle injury, so Williams will be given the chance to build on his impressive form for Scarlets this term.
With Jamie Roberts also absent, centre Scott Williams partners his Scarlets team-mate Jonathan Davies in midfield.
Rhys Priestland returns at fly-half after missing last season's entire Six Nations campaign with an Achilles injury.
And Cardiff Blues lock Bradley Davies will partner Alun-Wyn Jones in the second row, with Luke Charteris having to settle for a place on the bench.
British & Irish Lions flanker Dan Lydiate will make his first appearance for Wales since the summer of 2012, having missed nearly a year's international rugby because of injury.
Mike Phillips starts at scrum-half despite not currently having a club after he was sacked by Bayonne last week.
Wales: 15-L Halfpenny, 14-G North, 13-J Davies, 12-S Williams, 11-L Williams, 10-R Priestland, 9-M Phillips; 1-G Jenkins, 2-R Hibbard, 3-A Jones, 4-B Davies, 5-A W Jones, 6-D Lydiate, 7-S Warburton, 8-T Faletau.
Replacements: 16-K Owens, 17-P James, 18-S Andrews, 19-L Charteris, 20-J Tipuric, 21-L Williams, 22-J Hook, 23-A Beck