Powerful South Africa prop Ox Nche will play no further part in the side's five-match European tour, including the Test against Ireland, and has been replaced by Asenathi Ntlabakanye, who is awaiting a hearing on an alleged doping violation, SA Rugby said.
Nche, 30, was injured early in Saturday's 61-7 victory against Japan at Wembley Stadium and returned to South Africa on Sunday to undergo scans to determine the extent of the injury.
The Sharks forward twisted both his knee and ankle at a ruck and was on crutches after the game.
Ntlabakanye, who made his Test debut in July against Italy, had been in London playing for the Barbarians against the All Blacks XV at Twickenham on Saturday and joined up with the Springbok squad, which departed for France on Sunday.
The 26-year-old (above) had been left out of the South Africa squad in the Rugby Championship after being issued with two formal doping charges by the South African Institute for Drug-Free Sport.
SA Rugby in August said there had been an "adverse analytical finding" in random testing but that Ntlabakanye disputed committing a doping offence.
He is free to play until a hearing in December.
The Springboks take on France in Paris on Saturday in the second of five November Test matches.
They also play Italy on 15 November, Ireland on 22 November and Wales seven days after that.
Watch Ireland v Japan in the Quilter Nations Series on Saturday from 12pm on RTÉ2 and the RTÉ Player. Follow a live blog on the RTÉ News App and on rte.ie/sport. Listen to live commentary on RTÉ Radio 1 Extra
