Wallabies halfback Nic White is out of next month's Test series against France, while fellow veterans Matt To'omua and James O'Connor are also battling injuries, potentially robbing the side of almost 150 Test caps.
White has returned home to Canberra after suffering a MCL injury at training during their Gold Coast camp, and To'omua is already there with his injury being checked by Rugby Australia's chief medical officer, Warren McDonald.
To'omua is expected to rejoin the squad on Sunday with the Wallabies hopeful the playmaker will be available for the first Test on July 7.
O'Connor, who has carried the injury from Super Rugby Trans-Tasman, is being managed through training but the five-eighth is expected to play.
With White out, Queensland's Tate McDermott is now set for his first Test start after two matches off the bench, while Brumbies No.9 Ryan Lonergan is likely to make his debut.
Waratahs halfback Jake Gordon is in camp but is also recovering from a MCL injury and remains an outside chance of being available.
White doesn't require surgery and medical staff are hopeful he will be in the frame for the Bledisloe Cup with the first match on Aug. 7 in Auckland.
It comes as Rugby Australia push ahead with plans to play the opening match of the three Test series against France at the SCG despite the COVID-19 outbreak in Sydney.
The 42-man French squad arrived in Sydney on Tuesday night and underwent COVID-19 tests on Wednesday.
Les Bleus will be quarantined in their hotel for the next fortnight though they will be allowed out to train ahead of the Jul. 7 Test at the SCG.
The teams are playing a condensed series with three Tests in 11 days, the second at Melbourne's AAMI Park on Jul. 13 followed by the third at Suncorp Stadium in Brisbane on Jul. 17.
The second Test looked to be in most doubt, with Melbourne in lockdown for two weeks after a rise COVID-19 cases, but that has eased with crowds welcomed back to sporting events this weekend.
There were questions about whether that game would be shifted to Canberra, which could now be an option for the Sydney match should the pandemic continue to worsen on the eastern seaboard.
Queensland and Victoria have closed their borders to NSW residents from hotspot areas in the eastern suburbs and central Sydney.
RA chief executive Andy Marinos said they remained hopeful the matches would be played as scheduled.
"Appreciating that we continue to operate in a dynamic environment with COVID-19 impacts, we are moving ahead with our plans to host these matches as planned, subject to any further advice from our state government partners," Marinos said in a statement.
"We are now just two weeks away from the start of the series which kicks off with the Wallabies' first match at the historic Sydney Cricket Ground in 35 years.
"I want to thank (president) Bernard Laporte, (coach) Fabian Gautier and the FFR (French Rugby Federation) for their partnership in ensuring this series could go ahead.
"It has been a mammoth effort by all involved."