Australian captain Michael Clarke suffered a worrying recurrence of a hamstring injury as his side beat South Africa in the opening one-day international at Perth's WACA Ground on Friday.
In reply, South Africa threatened a record run chase at the venue when their skipper, AB de Villiers (80) and David Miller (65) put on 126 for the fifth wicket, but ultimately fell 32 runs short and were dismissed for 268.
Despite the efforts of de Villiers and Miller, the South Africans were always behind on the back foot after losing early wickets, with paceman Mitchell Johnson (2-38) celebrating his announcement as the ICC Cricketer of the Year by claiming both Proteas openers, Quinton de Kock and Hashim Amla, in quick succession.
Recalled wicketkeeper Matthew Wade claimed five catches in the South African innings, while man-of-the-match Nathan Coulter-Nile claimed 4-48.
The 33-year-old Clarke injured his troublesome left hamstring again as he made just 11 from 20 balls in the Australian innings and was immediately ruled out of taking any further part in the match.
Clarke has battled a degenerative back condition in recent years and hamstring troubles have plagued him, including missing matches on Australia's past two overseas tours, to Zimbabwe and the United Arab Emirates.
"Michael has reinjured his left hamstring and is currently being assessed," team doctor Peter Brukner said in a statement released by Cricket Australia.
"He will have a scan tomorrow and take no further part in the match."
The injury casts a significant cloud over his immediate playing future.
He is unlikely to play in the remainder of the one-day series, and the first Test against India is just three weeks away.
The World Cup, which is being co-hosted by Australia, starts in February.
The home side made the most of some good fortune with the bat, the Proteas dropping several catches, including grassing four chances to remove top scorer George Bailey, who made 70 from 75 balls as Australia rode their luck to recover from 144-5.
The Australian vice-captain should never have reached double figures.
Hit on the back by the first ball he faced from Dale Steyn, Bailey was dropped twice in successive deliveries he faced when he was on just two, as South Africa struck back with a vengeance following an opening stand of 94 by David Warner (46) and Aaron Finch (35).
David Miller dropped a sitter at point from the bowling of Morne Morkel, and then in the next over spinner Imran Tahir grassed a simple caught and bowled chance.
Bailey had two more lives on 38 and 47, the latter one also resulting in South African fielder Farhaan Behardien being forced from the field with a minor shoulder injury sustained in a diving attempt to complete the catch.
Bailey's luck came to an end when he skied a drive from the bowling of Steyn and was brilliantly caught by a back-pedalling Faf du Plessis at mid-off.
Seamer Vernon Philander led the way for the Proteas, claiming both the openers on his way to figures of 4-45 from his 10 overs.