Frans Steyn has been released by the Springboks at his own request and will not appear in Saturday's showdown with Wales at Kings Park in Durban.
The player advised SARU officials that he did not wish to be considered for the Series, with the Sharks centre explaining his shock decision.
"The environment in the Springbok squad is fantastic and I would like to state categorically that my relationship with Heyneke Meyer, the rest of the management and my team-mates is very good," said Steyn just days before the first Test.
Steyn - who is expected to take up a contract in Japan at the end of Super Rugby - said that he wished for time to reflect on his Springbok future. He indicated he would be available for the Sharks once the June internationals are completed.
"I have spoken at length to Frans and we are happy to accede to his request," said Jurie Roux, CEO of the South African Rugby Union (SARU).
"He has asked for some time to consider his international playing future and we must respect that. Let me make it clear that he has not retired from international rugby, but he has requested a break from it."
Roux added that Steyn had asked for privacy at this time.
"This is not an ideal situation, but, in other instances, sudden player absences through injury are not uncommon and I'm sure Heyneke and the selectors will adapt to his unavailability. Frans is now out of the squad and team management will respect his wish for privacy by not speculating on his decision or his likely return."