Australia replaced injured batsman Shaun Marsh with Phillip Hughes on Thursday while clearing fit-again paceman Jackson Bird to join the team in South Africa for the three-Test series starting on February 12.
Though named in the 15-man squad, both Marsh and Bird stayed put in Australia battling fitness issues.
"As Shaun Marsh's calf injury has not improved as much as required over the past four days he has been withdrawn from the Test squad for the tour of South Africa," national selector John Inverarity said in a statement.
"Phillip Hughes had been placed on standby and now comes into the Test squad as a replacement for Shaun. Phillip will head to South Africa as soon as possible."
Marsh injured his calf during Australia's one-day series against England and was undergoing treatment at Perth.
Bird, who injured his back in a Big Bash match last week, was cleared by the medical team after the 27-year-old paceman underwent bowling sessions at Hobart under coach Darren Lehmann's observation.
He, along with team-mate Moises Henriques, will fly to South Africa on Friday. After the first Test in Centurion, Port Elizabeth will host the second from February 20 while Cape Town is the venue for the third and final Test from March 1.