England will face an under-strength South Africa next month after Premiership Rugby reiterated its policy not to release English-based Springboks for the match.
It means South Africa will be without stars including Sale scrum-half Faf de Klerk and Wasps full-back Willie le Roux.
The match at Twickenham on November 3rd takes place outside World Rugby's international window.
World Rugby rules say clubs do not have to release players outside the window.
A spokesman for Premiership Rugby - the umbrella body for the top English clubs - told the BBC its policy "is only to release players under World Rugby Regulation 9".
Bath back-row forward Francois Louw, Gloucester lock Franco Mostert and Saracens prop Vincent Koch will also be unavailable to Springbok boss Rassie Erasmus.
All five players featured in last weekend's narrow 32-30 loss to the All Blacks by New Zealand, a game that confirmed South Africa's re-emergence as a rugby superpower following the victory over the All Blacks in Wellington three weeks earlier.