Bryan Habana and Victor Matfield have been ruled out of South Africa's World Cup clash against Fiji in Wellington on Saturday.
They are joined on the injury list by centre Jean de Villiers and his fellow back Butch James as the Springboks look to build from their 17-16 victory over Wales last weekend.
Lock Matfield has a hamstring injury, although there is some good news for South Africa with the return of his regular second-row partner Bakkies Botha after an Achilles problem.
Wing Habana has a leg injury, while De Villiers (rib cartilage) and James (hip) also miss out, with substitute lock Johann Muller facing a late fitness test on his hamstring.
Botha replaces Matfield in the starting line-up, Odwa Ndungane takes over from Habana and Frans Steyn moves from full-back to replace de Villiers, with Pat Lambie wearing the number 15 shirt.
"We have had injury problems at lock, but we have versatile players to cover for most situations," said Springboks coach Peter de Villiers.
"Danie Rossouw has now been picked to start at four, five, seven and eight this season, and he will call the lineouts this weekend.
"Against a tough proposition like Fiji you would prefer to have all your players available, but this is tournament rugby and we picked our squad knowing that we would have to cover for many situations."
SOUTH AFRICA: P Lambie; J P Pietersen, J Fourie, F Steyn, O Ndungane; M Steyn, F du Preez; G Steenkamp, J Smit (captain), J du Plessis, B Botha, D Rossouw, H Brussow, S Burger, P Spies.
Frustrated Flood is eager to prove Johnson wrong
Toby Flood is determined to prove England manager Martin Johnson was wrong to drop him for Jonny Wilkinson.
Flood, England's starting fly-half for their Six Nations title campaign, was axed for the opening Rugby World Cup victory over Argentina.
Even though Wilkinson missed five consecutive penalties and England struggled for momentum, Johnson kept a frustrated Flood rooted to the bench for the whole game, raising questions as to how far Flood's star has fallen since the Six Nations.
Flood is set to be given his chance in Sunday's clash with Georgia and has a point to prove.
"It was really frustrating not to be part of the first win," Flood said.
"They haven't said 'You're second fiddle or whatever', each week is selected on form more than anything else."