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Chairman of selectors John Inverarity on Sunday announced the 13-man squad to face Sri Lanka in the summer's first two ODIs, starting in Melbourne on Friday, with Hussey among several major absentees.
The Test trio of skipper Michael Clarke, David Warner and Matthew Wade were all rested from the start of the ODI program to give them a chance to recover from the rigours of a six-Test summer, while injured pair James Pattinson (side strain) and Shane Watson (calf) were not considered.
But Inverarity said fellow Test star Hussey, who had planning to retire from international cricket at the end of the summer, was omitted for the whole series because the selectors were looking to build toward the 2015 World Cup.
It means Hussey will play his last day of international cricket as the third Test against Sri Lanka heads to a finish at the SCG on Sunday.
"Michael has been a tremendous ODI player for Australia over a long period of time, a match-winner for his country and his presence in coloured clothing will be sorely missed," said Inverarity.
The squad has four potential debutants in batsmen Phil Hughes, Aaron Finch and Usman Khawaja and pace bowler Ben Cutting.
In Clarke's absence, Australia's Twenty20 skipper George Bailey will lead the team, while veteran Brad Haddin returns to take over the wicketkeeping duties.
"Michael (Clarke) has been battling a hamstring injury for a few weeks," Inverarity said.
"Matthew Wade and Brad Haddin are considered to be the two best keeper-batsmen in Australia," he said.
"Brad remains in consideration and he will play while Matthew has a break."
Inverarity said Hughes and Khawaja had earned a crack at the shorter form of the game, along with Finch.
"Phillip Hughes and Usman Khawaja are generally considered to be 'red-ball' cricketers, but their recent 50 over figures are most impressive," Inverarity said.
There was at least one Hussey in the squad, with David keeping his place as one of the experienced middle-order batsmen.
Allrounder Glenn Maxwell, in strong contention for a place in the Test squad to tour India in February, is expected to have a big role in the series.
Mitchell Starc headlines a pace attack boasting Cutting and Clint McKay.
Dean Jones will be added to the coaching staff for the first two ODIs as batting coach with Stuart Law deciding not to pursue the full-time batting coach role and returning to his job as Centre of Excellence high performance coach.
Australian squad: George Bailey (capt), Ben Cutting, Xavier Doherty, Aaron Finch, Brad Haddin, Phil Hughes, David Hussey, Usman Khawaja, Glenn Maxwell, Clint McKay, Steve Smith, Mitchell Starc.