Christian Lealiifano and Scott Sio will miss Australia's Rugby Championship opener against South Africa on Saturday due to injury .
The pair are among six players culled from the extended Wallabies squad and sent home by Michael Cheika.
Lealiifano was in contention to make his first Wallabies appearance in over three years following a battle with leukaemia.
However, a shoulder problem means he will not face the Springboks in Johannesburg this weekend as he and prop Sio (adductor) will return home for rehabilitation with a view to rejoining the squad for the meeting with Argentina in Brisbane on July 27.
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Jack Maddocks and Rob Valetini have been released by Cheika for club duties, while Tom Robertson needs a scan on an ankle injury that is expected to see him absent for both the Springboks and Pumas games.
Marika Koroibete is due to return home from South Africa following the birth of his second child, while uncapped prop Harry Johnson-Holmes will link up with the squad.
Cheika will name his XV on Thursday, ahead of the opening game of what will be a truncated Championship due to the Rugby World Cup beginning in Japan in September.