The world's leading one-day team will be without an entire battery of top-class pace bowlers when they take on their fourth-ranked challengers.
Mitchell Starc and Josh Hazlewood have been rested, while Nathan Coulter-Nile, James Pattinson, Pat Cummins, James Faulkner and Peter Siddle were ruled out by injury.
The touring squad includes three new fast bowlers in Daniel Worrall, who earned his first cap in Australia's nine-wicket win against Ireland in Benoni on Tuesday, Chris Tremain and Joe Mennie.
A key bowler for Australia could be leg-spinner Adam Zampa, 24, who made his debut in February and has taken 25 wickets in 13 matches, although South Africa's relatively small grounds and the thin air in Centurion and Johannesburg could challenge his skills.
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Australia coach Darren Lehmann said on arrival in Johannesburg last week that it was necessary to rotate the team's bowling resources with a view to building depth ahead of major Test series and one-day tournaments. He said all 14 members of the squad would get game time during the tour.
South Africa still have a strong batting line-up, however, led by Quinton de Kock, Hashim Amla and stand-in captain Faf du Plessis.
The South Africans have named an unusually large squad of 16 players and they too will have to juggle their resources, not only to provide opportunities for all their players but to comply with Cricket South Africa's recently-adopted racial 'targets' which call for a season's average of six players of colour, including at least two black African cricketers, in the national team.
The targets will make managing the workload of Rabada, 21, a particular challenge.
Rabada, named South Africa's cricketer of the year in July, has played in 34 of South Africa's 38 matches across all formats in the past year and there will be concerns about the risk of burn-out in a rare fast bowling talent.
SQUADS
South Africa: Faf du Plessis (capt), Kyle Abbott, Hashim Amla, Farhaan Behardien, Quinton de Kock (wkt), JP Duminy, David Miller, Wayne Parnell, Aaron Phangiso, Andile Phehlukwayo, Dwaine Pretorius, Kagiso Rabada, Rilee Rossouw, Tabraiz Shamsi, Dale Steyn, Imran Tahir.
FIXTURES
Sept 30: Centurion
Oct 2: Johannesburg
Oct 5: Durban
Oct 9: Port Elizabeth
Oct 12: Cape Town.
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