World Cup winners Faf de Klerk and Cheslin Kolbe have both been ruled out of South Africa's Autumn tests against Wales, Scotland and England.
Neither player has made a 32-man squad announced by SA Rugby, with Sale Sharks scrumhalf De Klerk sidelined by a hip injury and star wing Kolbe absent because of a knee problem.
No timescale has so far been put on De Klerk’s recovery, although some reports have claimed he could be out for up to five months.
Current world player of the year Pieter-Steph du Toit was also not considered as he continues his recovery from a shoulder injury.
"It's always unfortunate to lose players due to injury, but we have good depth in our squad and these are established players who have proven themselves at the highest level," Springboks head coach Jacques Nienaber told SA Rugby's website.
South Africa face Wales in Cardiff on November 6th, then tackle Scotland seven days later, followed by England at Twickenham on November 20th.
Frans Malherbe (neck) and Munster's RG Snyman (knee) are also out, with uncapped pair — lock Salmaan Moerat and scrumhalf Grant Williams — among those included.
Ulster's Duane Vermeulen and Munster centre Damian de Allende are also named, and there are four selected players based with English Premiership clubs in Leicester backrow forwards Jasper Wiese and Marco van Staden, Saracens prop Vincent Koch and Sale lock Lood de Jager.
Nienaber added: "The core group of players who played a key role in the series against the British and Irish Lions, as well as the Rugby Championship, will remain together as we build consistency and continuity in our squad with an eye on the 2023 Rugby World Cup.
“We had to travel to Australia (for the Rugby Championship) with an expanded squad due to the strict Covid-19 protocols in the country, but with the easing of travel restrictions to Europe and the UK, we were able to revert to a more manageable touring squad.
“We are two years out from the Rugby World Cup in France, and we have close to 20 Test matches before we start our defence of the title, so every match will count in terms of building confidence and consistency as a group.
“England is in fourth place on the world rankings, and Scotland and Wales are in seventh and ninth place respectively, and they are all top-class teams that will want to make a strong statement in front of their home crowds.
“We will need to get into the swing of things quickly when we assemble.”