Springbok inside centre Frans Steyn and prop Coenie Oosthuizen have been ruled out of Saturday's Test against the Wallabies.
Steyn rolled his ankle in training in Pretoria on Monday and has been an injury doubt all week. He failed a fitness test at Friday's captain's run.
Captain Jean de Villiers moves to number 12 with Lions youngster Jaco Taute set to make his international debut in the outside centre channel.
Juan de Jongh takes Taute's place on the bench. Oosthuizen, who was named on the bench, has been replaced by Pat Cilliers.
"Coenie, who played 35 minutes of rugby for the Free State Cheetahs last weekend, had stiffness in the neck and shoulder area after the game," said Bok coach Heyneke Meyer.
"After sitting out training on Monday, he felt much better and took part in the field sessions on Tuesday and Wednesday, but based on the nature of his injury and the initial symptoms early in the week, we felt that it would be better to withdraw him from the Test.
"Coenie is a young player who has a lot of rugby ahead of him and with injuries like these it's always better to gradually build him back to full match fitness."
Commenting on the injuries, Springbok coach Heyneke Meyer said: "Losing Frans and Coenie so close to the Test is a big setback, but we will always consider player welfare first. I'm very excited to see what Jaco will bring to this team and it's great to have an experienced player like Juan as back-up. Pat has been part of this squad for almost two months now and he will slot in easily."
The Springboks will be playing with black arm bands on Saturday and a minute's silence will be observed in the stadium before kick-off to commemorate the life of Malome Maimane, the Springbok Technical Adviser from 2008 to 2011, who recently passed away.
South African (revised): 15 Zane Kirchner, 14 Bryan Habana, 13 Jaco Taute, 12 Jean de Villiers (captain), 11 Francois Hougaard, 10 Johan Goosen, 9 Ruan Pienaar, 8 Duane Vermeulen, 7 Willem Alberts, 6 Francois Louw, 5 Andries Bekker, 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Adriaan Strauss, 1 Tendai Mtawarira.
Replacements: 16 Tiaan Liebenberg, 17 Pat Cilliers , 18 Flip van der Merwe, 19 Marcell Coetzee, 20 Elton Jantjies, 21 Juan de Jongh, 22 Pat Lambie.
Date: Saturday, September 29
Venue: Loftus Versfeld, Pretoria
Kick-off: 17.00 (15.00 GMT ; 01.00 NSW/ACT)
Weather: Dry. Clear skies, 21°C
Referee: Alain Rolland (Ireland)
Assistant referees: Romain Poite (France), Greg Garner (England)
TMO: Shaun Veldsman (South Africa)