Glenn Maxwell described himself as "shattered" after being told he requires elbow surgery, ruling him out of Australia's tour of South Africa.
The all-rounder will undergo an operation on his left arm on Thursday, with his spot in the ODI and T20 squads taken by D'Arcy Short.
Maxwell had been recalled by his country for the first time since taking a break from cricket in October to concentrate on his mental health, but he now faces up to eight weeks on the sidelines.
After the news was confirmed by Cricket Australia, Maxwell wrote on Twitter: "Shattered to be missing the South Africa tour. I wish all the lads the best of luck over there and I'll be watching from home!
"Thanks for all the wishes of support."
The Wallabies face three T20s and three ODIs against the Proteas, with Maxwell's absence coming after an injury he carried in the closing weeks of the Big Bash League season.
The 31-year-old helped Melbourne Stars to the final of that competition, where they lost to Sydney Sixers.
National selector Trevor Hohns lamented the loss of Maxwell but is confident Western Australia's Short can fill the void.
"We are disappointed to lose Glenn this close to the tour as we were looking forward to welcoming him back to the national side in both the 20- and 50-over formats after his break during the summer," Hohns said.
"Unfortunately, the pain he has experienced in the elbow in the latter stages of the BBL increased over the weekend and he will have surgery immediately to rectify the situation.
"An opportunity has now presented itself for D'Arcy and we're confident he'll make the most of whatever opportunities come his way in South Africa."