Ange Postecoglou has injury and fitness concerns ahead of the clash in Sydney, and is unwilling to take too many risks ahead of the FIFA World Cup.
Several spots in the Socceroos' final 23 remain up for grabs, with Postecoglou to cut his squad to 27 on Tuesday before they leave for Brazil a day later.
Captain Mile Jedinak (groin), attacking midfielder Tom Rogic (groin) and centre-back Curtis Good (hip flexor) are unlikely to play against South Africa.
Josh Kennedy, Mitch Langerak and Dario Vidosic, who arrived in camp late, may also be left out.
Australia assistant Ante Milicic said no risks would be taken for the friendly at ANZ Stadium.
"He (Postecoglou) doesn't need to risk anybody who's got any question marks (over their fitness)," Milicic said on Friday.
"It's not a game where we have to risk any players and there's probably players that he wants to see a little bit more than others and he'll make that call."
Fighting for places in the final 23, Preston North End defender Bailey Wright and Jeonbuk Motors centre-back Alex Wilkinson will be out to impress.
The likes of Massimo Luongo, James Holland, Oliver Bozanic and Adam Sarota are also likely to get some game time.
A-League Golden Boot winner Adam Taggart will be eager to stake his claim, while the nation's all-time leading goalscorer in Tim Cahill is sure to play his part.
South Africa's plans for their friendlies against Australia and New Zealand were ruined with 11 players pulling out of the initial squad.
Due to a combination of injuries and clubs unwilling to release players, South Africa coach Gordon Igesund was forced to hastily rebuild his squad with seven players brought in before the team flew out of Johannesburg on Tuesday.
Igesund's side will take on Australia then travel to Auckland to play New Zealand on May 30.
Kagisho Dikgacoi (Crystal Palace), Siyanda Xulu (Rostov), Andile Jali (Oostende), Siphiwe Tshabalala, Bernard Parker, Tsepo Masilela and Itumeleng Khune (all Kaizer Chiefs) did not travel.
South Africa have won 11 of the 20 matches played between the two countries, but another victory looks unlikely given their absences.
