The Wallabies have been hit with another blow a day before their test against the Springboks, with star No 8 David Pocock being ruled out because of a concerning neck injury.
Pocock was unable to recover from ongoing neck soreness and stiffness he suffered during the Wallabies' second Bledisloe Cup loss against the All Blacks last month.
The exact nature or extent of Pocock's neck issues were not revealed, but he was not able to participate in contact drills in training this week.
Former Crusader Pete Samu - who isn't a noted no 8 - will replace the injured star in the Wallabies' starting lineup.
Head coach Michael Cheika hasn't commented on Pocock's injury, but after naming him in his initial team on Wednesday, he said the Wallabies team needed to protect Pocock a bit more at the breakdown.
Meanwhile, Cheika has taken on of the biggest selection gambles of his coaching career by dropping star first-five Bernard Foley to the bench for the first time in his 51-test career, electing to start with Kurtley Beale in the playmaker's role instead.
"I'm not looking to mix and match for the sake of it," Cheika said. "It's a big test for us. I think this is the best combination for us to go into this game.
"I thought Kurtley deserves an opportunity back in the 10 jersey. He's had it before and I think he's matured a lot as a player and person and I certainly trust him to be in charge of the team there."
Cheika's purpose in dropping Foley and entrusting the first-five role to the veteran utility player isn't entirely clear. In naming Matt Toomua in Beale's place at inside center, he gives himself the option of continuing the two playmaker setup which has been a feature of his coaching style.
Whether he is right to have confidence in Toomua, who has just returned to Australian rugby after a long stint in England, will be decided on Saturday.
"Toomua has come back with a lot of confidence and he likes the shape of the game and he fits into it quite nicely," Cheika said. "I'd like to get on the front a bit more in attack and throw out a bit of a challenge there and give the opportunity to Toomua and Beal and then see how the other lads respond."
Beale has a powerful kicking game and poses a significantly better running threat than Foley at first receiver, especially from phase play. That might bring a challenge of unpredictability to the Springboks defense which was far from perfect in its most recent 32-19 loss to Argentina.
The Wallabies have lost six of their last seven tests, including 38-13 and 40-12 defeats by New Zealand in the first two matches of the Championship. A loss to the Springboks would see Australia drop below South Africa and Scotland to seventh place — its lowest spot since world rankings began in 2003.