Jess Jonassen has suffered a fresh hamstring injury just two months out from the Twenty20 World Cup.
Jonassen was hurt in Australia's T20 win over India in Mumbai on Friday, and scans have since shown a strain.
The left-arm orthodox bowler has now been sent home for rehabilitation on the injury, with legspinner Amanda-Jade Wellington called in to replace her.
"It's evident that the timeframes required for a return during this series are too short," Australia's physio Kate Beerworth said in a statement.
"Jess will be unavailable for the remainder of the series and will return to Brisbane to continue her rehab."
Jonassen was part of Australia's T20 World Cup success at home in 2020, but missed out on playing a game in the 2018 victory as she battled back from a knee injury.
Provided she is fit, she will form a crucial part of Australia's bowling attack in South Africa in February.
Wellington's call up comes after she was initially excluded from the squad for India in a significant blow to her chances of being picked for the World Cup.
Australia have several spin options, with legspinner Alana King having proven herself a force in world cricket in the past year.
Fellow wrist-spinner Georgia Wareham has a chance of returning from a long-term knee injury in coming weeks for Victoria.
Spinning allrounder Sophie Molineux has also previously been a fixture in the national team, but was recently sidelined by a ruptured ACL.