Wales will be without captain Alun Wyn Jones and loose-forward Ross Moriarty for the remainder of the autumn international series after they were ruled out for "a number of months" on Tuesday.
Welsh Rugby have confirmed the pair will both need surgery, lock Jones for his troublesome shoulder and Moriarty after he was also injured in the 54-16 mauling by New Zealand on Saturday.
Back row Taulupe Faletau was the third player sidelined for the remainder of the series this month. His ankle injury will keep him out of the games against South Africa on Saturday, and then Fiji and Australia on consecutive weekends after that.
Shane Lewis-Hughes, who can play lock or as part of the back-row, and uncapped lock Rhys Davies have been called into the squad.
Scrumhalf Tomas Williams believes Wales have leaders in their squad to step into Jones’s shoes for the next three tests.
"Obviously, he'll be a big loss. He's a big leader, but other boys will have to step up," Williams told reporters on Tuesday.
Better news for coach Wayne Pivac is the return from COVID-19 isolation of centre Willis Halaholo, and Williams says the team must stay positive ahead of the weekend meeting with the world champions.
"We have done our reviews and seen what we need to work on. There were a couple of good parts (against New Zealand)," Williams said.
"We have to move on pretty quickly, the best thing is to take the positives and turn our attention to South Africa."
The Boks have injury worries of their own, selecting scrumhalf Herschel Jantjies in place of sidelined Faf de Klerk, with Cobus Reinach on the bench.
"Everyone knows how good he (De Klerk) is, but the other two are good nines and both have their qualities. I don’t know if it will change their game-plan too much," Williams said.
"They will be physical, there are no ifs or buts about that. But we are confident we can match that."
(Reporting by Nick Said, editing by Ed Osmond)