Scrum-half Fourie du Preez is out of the South Africa squad to face Wales in Cardiff on Saturday, 24 November.
Du Preez has been dogged by a recurring shoulder injury
His absence means a total of 13 of the Springboks' World Cup-winning squad are unavailable for the tour which also sees them play the Barbarians.
Du Preez has a shoulder problem, while Victor Matfield withdrew last week to spend more time with his family.
Other absentees include Wikus van Heerden, Danie Rossouw, Gurthro Steenkamp and Percy Montgomery.
They are due to club commitments, while Clermont Auvergne have refused Springbok captain John Smit permission to face the Baa-Baas at Twickenham on 1 December.
The hooker should be available to take on Wales at the Millennium Stadium on Saturday.
Prop BJ Botha and centre Jean de Villiers are missing through injury, while Prop Os du Randt and number eight Bob Skinstad have retired.
It means uncapped duo, prop Wian du Preez and number eight Ryan Kankowski, and twice-capped flanker Hilton Lobberts come into the squad.
The trio were called up after loose forwards Danie Rossouw (neck) and Wikus van Heerden (neck) and prop Gurthro Steenkamp (hand) pulled out of the squad on Monday.
Revised South Africa squad: John Smit (captain), Bakkies Botha, Schalk Burger, Bismarck du Plessis, Jannie du Plessis, Fourie du Preez, Wian du Preez, Jaque Fourie, Bryan Habana, Conrad Jantjes, Ricky Januarie, Wayne Julies, Ryan Kankowski, Hilton Lobberts, Johann Muller, Akona Ndungane, Wynand Olivier, Ruan Pienaar, JP Pietersen, Andr Pretorius, Juan Smith, Francois Steyn, Albert van den Berg, CJ van der Linde, Heinke van der Merwe.