Francois Steyn's shock decision to walk away from international rugby has left South Africa vulnerable at centre as it looks to extend a proud record against Wales in Saturday's (Sunday NZ time) first test.
With Steyn released from the squad at his own request on Tuesday, and with Juan de Jongh ruled out through illness, coach Heyneke Meyer was forced to name an inexperienced centre pairing in Jan Serfontein and JP Pietersen.
Steyn has not given an official reason for taking a break from international rugby, but South African newspapers claimed he had quit due to a financial dispute with the South African Rugby Union revolving around image rights.
"I'm a little bit disappointed that he's not available, but I respect his decision," Meyer said.
While Serfontein will be making his first start for the Springboks, Pietersen has played 49 of his 51 tests at wing and the other two at fullback.
The duo is likely to face a stern test from opposite numbers Jamie Roberts and Jonathan Davies, who form one of the finest midfield partnerships in world rugby.
"I still believe JP can be a great centre, but we have lost five world-class centers and now we find ourselves thin on outside centers a year before a World Cup," Meyer said.
"Jan has played nine games from the bench, including one against New Zealand. It will be a hell of a test for him because I really rate Roberts as one of the best centres in the world."
South Africa is still the strong favourite for the first test, having won 27 of their 29 tests against Wales.
Prop Gurthro Steenkamp will win his 50th test cap for the Springboks after being picked ahead of Tendai Mtawarira, while Cornal Hendricks will make his debut on the wing.
Wales warmed up for the two-match series with a 34-12 win over the Eastern Province Kings in Port Elizabeth on Tuesday, and have named uncapped players Gareth Davies and Matthew Morgan on the bench.
"There were a couple of tough calls to make, but it's great guys like Gareth and Matthew have a chance after putting their hands up," Wales coach Warren Gatland said.
Prop Adam Jones was rested for Tuesday's game along with a host of other senior players, but will return to make his 100th international appearance. Jones has played 94 times for Wales, and five times for the British and Irish Lions.
Flank Dan Lydiate will take his place in the back row after proving his fitness by playing 80 minutes against the Kings following a long injury layoff.
"A lot of this side have experienced playing over here before in big games and this week is no different, it's going to be a brilliant occasion, the atmosphere will be electric and hopefully it will be a great test match," Gatland said.
SOUTH AFRICA: Willie le Roux, Cornal Hendricks, JP Pietersen, Jan Serfontein, Bryan Habana, Morne Steyn, Fourie du Preez; Duane Vermeulen, Willem Alberts, Francois Louw, Victor Matfield (captain), Bakkies Botha, Jannie du Plessis, Bismarck du Plessis, Gurthro Steenkamp. Reserves: Schalk Brits, Tendai Mtawarira, Coenie Oosthuizen, Lood de Jager, Schalk Burger, Ruan Pienaar, Johan Goosen, Lwazi Mvovo.
WALES: Liam Williams, Alex Cuthbert, Jonathan Davies, Jamie Roberts, George North, Dan Biggar, Mike Phillips; Taulupe Faletau, Aaron Shingler, Dan Lydiate, Alun-Wyn Jones (captain), Luke Charteris, Adam Jones, Ken Owens, Gethin Jenkins. Reserves: Matthew Rees, Paul James, Samson Lee, Ian Evans, Josh Turnbull, Gareth Davies, James Hook, Matthew Morgan
Which rugby player who's off overseas would you most like to see back playing in NZ?