Duminy was withdrawn from the series, which begins in Perth on Friday, with patella tendinopathy in his left knee, a team spokesman said.
Farhaan Behardien, who is in Australia for the T20 series, will replace him in the squad, while Marchant de Lange has been added to bolster their pace-bowling resources.
“JP aggravated his long-standing knee injury during the current T20 series against Australia,” Proteas team manager Mohammed Moosajee said.
“This is the same injury that plagued him during the tri-series in Zimbabwe and caused him to miss the Champions League T20.
“The recommendation from the medical committee is that he returns back to South Africa for a six-week period of rest and rehabilitation, particularly ahead of a busy season at home and the ICC World Cup in three months.”
South Africa’s ODI squad will gather in Perth later Monday, ahead of the first match at the WACA on Friday.
Duminy scored just two runs as Australia won the deciding T20 by two wickets with one ball to spare in Sydney on Sunday.
Cameron White steered the Australians home with an unbeaten 41 off 31 balls to pip the Proteas in a tense decider at Olympic Stadium- AFP