Nortje was sidelined from September 2023 for nine months after suffering a stress fracture, although he recovered to play for South Africa in the T20 World Cup, where they reached the final in June.
He has now suffered a toe injury that will leave him sidelined for the second and third T20 matches and the entire ODI series, which is an important warm-up for next year's ICC Champions Trophy.
Scans on Wednesday revealed a fracture and Nortje will now consult doctors to determine what treatment is needed, a Cricket South Africa statement said.
Uncapped all-rounder Dayyaan Galiem has been named as replacement for the remaining two T20 fixtures in Pretoria on Friday and at the Wanderers in Johannesburg on Saturday.
Having rested several of their regular players for the shortest-format series against Pakistan, the big guns are back for the ODI games.
Batters Temba Bavuma, Tristan Stubbs and Aiden Markram make a return, along with allrounder Marco Jansen, seamer Kagiso Rabada and left-arm wrist-spinner Tabraiz Shamsi.
South Africa have also included 18-year-old firebrand fast bowler Kwena Maphaka, who gets a maiden 50-over call-up.
The one-day series begins in Paarl on Tuesday.
SOUTH AFRICA ODI SQUAD:Â
Temba Bavuma (captain), Ottneil Baartman, Tony de Zorzi, Marco Jansen, Heinrich Klaasen, Keshav Maharaj, Kwena Maphaka, Aiden Markram, David Miller, Andile Phehlukwayo, Kagiso Rabada, Tristan Stubbs, Ryan Rickelton, Tabraiz Shamsi, Rassie van der Dussen
