South Africa captain Warren Whiteley has been ruled out of their end-of-year tour of Europe after doctors said his groin injury would take two more months to heal.
Eben Etzebeth will lead the Springboks in his absence in tests against Ireland, France, Italy and Wales in November and December, SA Rugby said on Thursday.
Whiteley was injured in the build-up to the last Test against France in June's three-match series and missed the entire Rugby Championship.
He had been initially expected to return for the final games of the annual southern hemisphere championship, but is now set to be fit before the start of the next year's Super Rugby season in February.
South Africa will also have to do without French-based loose forward Duane Vermeulen, who is still recovering from surgery on a groin injury, and the Lions duo of flanker Jaco Kriel and wing Ruan Combrinck, who both underwent shoulder surgery in recent weeks.
Stormers prop Frans Malherbe, who has a long-term neck injury, is also out.
Prop Coenie Oosthuizen, who suffered a fractured arm against Australia in Perth at the beginning of September, is available, as is No.8 Uzair Cassiem, who sustained a rib injury against the Wallabies two weeks ago in Bloemfontein.
The Springboks squad will be confirmed on October 29, the day after the Currie Cup final brings the domestic season to a close.
South Africa take on Ireland in Dublin on November 11, then France in Paris one week later, followed by Italy in Padova on November 25 and Wales in Cardiff on December 2.