Samu Kerevi will miss Australia's Test against Japan on Saturday with the barnstorming centre ruled out with an ankle injury in a huge blow for the Wallabies.
Hunter Paisami will replace Kerevi in the No.12 jersey in his first match back since the All Blacks in August, when he left the Wallabies squad for the birth of his child.
Kerevi then proved impossible to dislodge during the Rugby Championship where he played a massive part in their four successive victories over world champions South Africa and Argentina.
However, he suffered a high ankle sprain in the Wallabies' final 32-17 win over the Pumas on the Gold Coast earlier this month.
Returning for his first Tests since the 2019 Rugby World Cup, 38-Test Kerevi's explosive ability to get across the advantage line in the midfield was key to Australia's winning run.
The Wallabies will name their line-up later Thursday for the match in Oita, which was the scene of their World Cup quarter-final exit.
The Australians were sent packing under the dome there by England.
Quade Cooper is expected to retain the No.10 jersey for the match but appears unlikely to continue on to the UK for the remaining Tests against Scotland, England and Wales.
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Cooper, who has also been a revelation since returning to the Wallabies fold, is in a tug-of-war between the Wallabies and his Japanese club Kintetsu.
Kerevi, who is contracted to Japanese club Suntory Sungoliath, was also part of Australia's Rugby Sevens Olympic campaign in Tokyo and is no certainty to travel on.
Another Japanese-based star, flanker Sean McMahon, left immediately after the Rugby Championship to re-join his family and will miss the match after being granted permission to leave their bubble.