Brighton forward Percy Tau is among six South Africans ruled out of an international friendly against Uganda in Soweto on Thursday after testing positive for Covid-19.
A national football association statement said defender Mosa Lebusa and midfielders Rivaldo Coetzee, Sipho Mbule, Tebogo Mokoena and Mothobi Mvala were the other withdrawals from a 19-strong squad.
Assistant coaches Cedomir Janevski and Helman Mkhalele have called up four uncapped players, Denwin Farmer, Evidence Makgopa, Njabulo Ngcobo and Ethan Brooks, as replacements.
Macedonian Janevski and former South Africa star Mkhalele are part of a new coaching team, but head coach Hugo Broos will be missing having returned home to Belgium for his second Covid-19 injection.
South Africa and Uganda, ranked 75th and 84th respectively in the world, are desperate for a morale-boosting victory after both failed to qualify for the 2021 Africa Cup of Nations in Cameroon.
Uganda also changed coaches recently, ditching Northern Ireland-born Johnny McKinstry and appointing local Abdallah Mubiru as caretaker boss.
Both countries are preparing for 2022 World Cup qualifying from September. South Africa meet Ghana, Zimbabwe and Ethiopia in Group G and Uganda face Mali, Kenya and Rwanda in Group E.