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The Springboks have only lost once to Wales, in 1999, but will be without several first-choice stars for the Prince William Cup clash at the Millennium Stadium.
Rugby World Cup-winning flyhalf Butch James is the latest to withdraw from the team after losing his club-versus-country battle to be released for the game that falls outside the IRB's Test window.
James, initially named at centre, plays his club rugby at Bath and has been refused permission to play in a fixture by Premier Rugby, the governing body for the Premiership.
South Africa rugby bosses are to raise their objections about the alleged "inconsistency" of current regulations but coach Peter de Villiers, who will instead hand Stormers centre Juan de Jongh his first cap, remained philosophical about his options.
"Life moves on. Everything that happens in life is for a good reason, but we just have to wait to see what that good reason is. The loss of Butch means we can give an amazing opportunity to another young player," De Villiers said.
"It is hard to say what the future will now hold for Butch. We know what he can offer us but we will wait and see how the youngster goes on Saturday. Why fix things if they're not broken?
"Juan has shown all the potential to go further in his career. Now we are throwing him into the deep end and we will see how he goes.
"But there is no such thing as a weak Springboks team. We don't give away the colours, people have to earn them and when they pull on that jersey, they will always given everything for their country.
"We are blessed to be able to replace players with others of such calibre."
De Jongh, 22, impressed during the Stormers' passage to the Super 14 final and has thrived alongside Jaque Fourie, who he partners on Saturday.
However, he faces a potential baptism of fire against Wales inside centre Jamie Roberts, named Player of the Series against the Springboks for the British Lions last year.
"I saw a lot of Roberts during the Lions tour. He's a big and physical player and I'm looking forward to that challenge," De Jongh said.
"Roberts is Wales' first choice but I've come up against big guys all season. Size is not everything, so I'm not thinking too much about that.
"In my first Test, my only focus is on fitting in well with the team."
De Jongh joins fellow Stormers, wing Gio Aplon and flank Francois Louw, in winning their first Springbok cap in a team that features four European-based players.
They include fullback Francois Steyn and one-time golden boy Joe van Niekerk, both now playing in France.
Wales are also without Lions quartet Shane Williams, Andy Powell, Gethin Jenkins and Martyn Williams, while 18-year-old wing Tom Prydie, who became Wales youngest ever international in this year's Six Nations, makes only his second Test appearance.
"We have always said that if we are to be able to consistently compete with the best teams in the world then we must play them as often as possible," said head coach Warren Gatland.
"We had a disappointing Six Nations but the feeling was that we were not very far from becoming a very tough team to beat. We are confident that we can beat these top teams."
Teams:
Wales:
15. Lee Byrne, 14. Leigh Halfpenny, 13. James Hook, 12. Jamie Roberts, 11. Tom Prydie, 10. Stephen Jones, 9. Mike Phillips, 8. Ryan Jones (captain), 7. Sam Warburton, 6. Jonathan Thomas, 5. Deiniol Jones, 4. Bradley Davies, 3. Adam Jones, 2. Matthew Rees, 1. Paul James
Substitutes: 16. Huw Bennett, 17. John Yapp, 18. Alun Wyn Jones, 19. Rob McCusker, 20. Richie Rees, 21. Dan Biggar, 22. Andrew Bishop
South Africa:
15. Frans Steyn, 14. Gio Aplon, 13. Jaque Fourie, 12. Juan de Jongh, 11. Odwa Ndungane, 10. Ruan Pienaar, 9. Ricky Januarie, 8. Joe van Niekerk, 7. Dewald Potgieter, 6. Francois Louw, 5. Victor Matfield, 4. Danie Rossouw, 3. BJ Botha, 2. John Smit (captain), 1. CJ van der Linde
Substitutes: 16. Chiliboy Ralepelle, 17. Jannie du Plessis, 18. Alistair Hargreaves, 19. Ryan Kankowski, 20. Meyer Bosman, 21. Zane Kirchner, 22. Bjorn Basson
Kick-off: 15:30
