Star winger Marika Koroibete will miss the Wallabies' entire northern hemisphere spring tour after opting to stay in Australia following the birth of his third child.
Coach Dave Rennie said Koroibete needed precious family time before linking with Japan's Panasonic Wild Knights next season on a lucrative multi-year contract.
"We've been discussing it for a while," Rennie said.
"We let him go home a week early during The Rugby Championship. COVID has thrown a lot of curve balls at all of us. Obviously, Marika has been away from home for a long time.
"(His wife) Emma's pretty isolated down there. They've had a newborn baby, and a couple of other young boys. Based on those situations, Marika has chosen not to tour."
It's uncertain when - or if - the 2019 John Eales Medallist will play for the Wallabies again.
Koroibete's 42 Test caps are not enough to make him eligible for selection from overseas under the Giteau Law, but Rugby Australia has loosened that restriction in recent times.
In the short term, at least, Rennie will likely opt for either Jordan Petaia or Tom Wright to fill Koroibete's boots.
"As always, it's an opportunity, isn't it? Marika didn't play the last game. Jordy got the start," the coach said.
"It gave Tom Wright a sniff, and he played really well. It's a position we have a bit of depth in.
"Marika is an unbelievable player with a massive work ethic. And physicality. Big shoes to fill, but we have good depth there."
The 29-year-old is not the only big-name omission from next weekend's tour-opening Test against Japan, with recently returned back-rower Sean McMahon temporarily out of the squad's bubble for family reasons.
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McMahon went back to Japan to be with his family following The Rugby Championship, while centre Samu Kerevi is doubtful while nursing a syndesmosis injury suffered in Australia's final match with Argentina.
Rennie says the Wallabies are working closely with both players' Japan-based clubs regarding World Rugby's regulation nine rule, to navigate their selections for the ensuing trip to Europe.
"Obviously we've been talking to both clubs and the relationship side of it is key for us," Rennie said on Sunday.
"Technically, from a 'reg' nine perspective, players have to be released for national duty.
"But, we're also conscious that we want to build a strong relationship with a club so we're talking through that at the moment."
Rennie said having players like Kerevi, McMahon and fellow Japan-based star Quade Cooper was important for his side as they build momentum two years from the World Cup.
The importance of regulation nine is also shown through their competitors like South Africa, who predominantly choose their side from overseas clubs, Rennie added.
Adding to the list of players missing the tour is prop Pone Fa'amausili, who has tweaked his calf and won't be touring, according to Rennie.