Springboks boss Rassie Erasmus has been dealt a major injury blow after four key players were ruled out of November's Nations Championship matches.
Cheslin Kolbe, Eben Etzebeth, Handre Pollard and André Esterhuizen will all miss the tour through injury.
Their absence comes as South Africa prepare to face Italy, France and Ireland before the Nations Championship Finals Weekend in London.
Erasmus has named a 37-man squad, with six uncapped players handed their first official Test call-ups.
Yaqeen Ahmed, Sebastian de Klerk, Luan Giliomee, Markus Muller, Riley Norton and Emmanuel Tshituka are all included.
Captain Siya Kolisi, Pieter-Steph du Toit and Damian de Allende are among the experienced stars who retain their places.
Four Springboks stars ruled out through injury
The loss of Kolbe, Etzebeth, Pollard and Esterhuizen leaves Erasmus without four World Cup winners.
Esterhuizen is the latest concern after suffering an injury during the Sharks' win over Cardiff.
The powerful centre was forced off in the opening minute and was later seen on crutches wearing a protective boot.
Erasmus admitted losing such experienced players was a setback.
"It's always sad to lose players of that calibre, but we are pleased with the cover we have in those positions, and it also offers other players the opportunity to put up their hands," he said.
Six uncapped Springboks handed surprise call-ups
Erasmus has turned to six new faces as he looks to build squad depth.
All six have spent time in the wider Springboks set-up.
Ahmed, Giliomee, Muller and Tshituka have represented South Africa A, while Norton featured against the Barbarians earlier this year.
De Klerk previously attended a national alignment camp.
"We've had all six players on our radar for a while now, and they've delivered consistently for their respective franchises in the last two seasons, so they thoroughly deserve their call-ups," Erasmus said.
"Building squad depth has always been one of our key pillars as a team."
Springboks squad in full
Props: Thomas du Toit, Ox Nche, Wilco Louw, Ntuthuko Mchunu, Zachary Porthen, Gerhard Steenekamp.
Hookers: Malcolm Marx, Jan-Hendrik Wessels.
Locks: Lood de Jager, Salmaan Moerat, Ruan Nortje, Riley Norton, Franco Mostert.
Loose forwards: Paul de Villiers, Siya Kolisi, Cameron Hanekom, Emmanuel Tshituka, Jasper Wiese.
Utility forwards: Pieter-Steph du Toit, Marco van Staden.
Scrum-halves: Cobus Reinach, Morne van den Berg, Grant Williams.
Fly-halves: Yaqeen Ahmed, Sacha Feinberg-Mngomezulu, Luan Giliomee, Manie Libbok.
Centres: Damian de Allende, Jesse Kriel, Markus Muller, Canan Moodie.
Outside backs: Sebastian de Klerk, Aphelele Fassi, Ethan Hooker, Edwill van der Merwe, Kurt-Lee Arendse, Damian Willemse.
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Springboks November fixtures
- 7 November: Italy v South Africa
- 13 November: France v South Africa
- 21 November: Ireland v South Africa
- 27–29 November: Nations Championship Finals Weekend, London
South Africa currently sit top of the Southern Hemisphere standings on points difference, level with New Zealand on 15 points.
Erasmus knows his side face a tough run of matches.
"This is an intense competition and every point counts," he said.
"We have a big job ahead, and it will be important to hit the ground running."
With four established stars missing, the next month could offer a huge chance for South Africa's next generation to make their mark.
