Injury has cost Josh Kennedy and Tom Rogic a place in the Socceroos' 23-man World Cup squad, with fourth-choice goalkeeper Mark Birighitti and defender Luke Wilkshire the other players axed.
Kennedy has been struggling with a back problem and missed the 2-0 friendly win over Parana Clube on Monday, a game which Rogic started before being withdrawn at half-time.
The attacking midfielder has been battling a groin problem since April and was unable to justify his selection in Ange Postecoglou's final squad.
Missing the World Cup is cruel blow to veteran striker Kennedy, who scored the winning goal in the final qualifier against Iraq to send Australia to Brazil.
"Every step of the selection process has been difficult because the players have worked very hard since they came into camp but we have had to weigh up form, fitness and squad balance in coming up with the 23 players who will represent Australia at the 2014 World Cup," Postecoglou said in a statement
With Mat Ryan set to start in goal and Mitch Langerak and Eugene Galekovic supplying cover, Birighitti's exclusion comes as no surprise, but the omission of Wilkshire is somewhat unexpected.
The experienced fullback was expected to provide cover for right-back Ivan Franjic, who picked up a knee knock in the farewell friendly against South Africa in Sydney last month.
The injuries to Rogic and particularly Kennedy have offered something of a reprieve to 21-year-old Newcastle Jets striker Adam Taggart, who had been expected to be sent home despite his golden boot-winning season in the A-League.