Ms Edwards served as acting secretary of the department from February last year, leading the department as the country responded to the COVID-19 pandemic.

The announcement of her departure comes just weeks after Secretary of Foreign Affairs and Trade Frances Adamson confirmed her long-rumoured jump from the upper echelon of the bureaucracy to take up the role as governor of South Australia.

The role of associate secretary was a unique position with Ms Edwards and Professor Brendan Murphy at the helm of the department, and it remains to be seen whether Ms Edwards will be replaced in that role specifically.

If Ms Edwards is to be replaced as associate secretary, it gives the government three empty seats to fill at the top levels of the public service.

As well as Ms Adamson's role at the top of Foreign Affairs and Trade, the government is yet to replace Chris Moraitis, who left his role as secretary of the Attorney-General's Department to take on the job leading the Office of the Special Investigator investigating alleged war crimes in Afghanistan.

A long list of names has been rumoured to be in the running for the role of Australia's top diplomat, with ripples to be felt throughout other departments.

Defence Secretary and former DFAT deputy secretary Greg Moriarty and former ambassador Paul Grigson, who currently heads up the Vaccine Strategy Integration section at Prime Minister and Cabinet have both been repeatedly connected to the role, along with secretaries of other departments and deputy secretaries within the department itself.

The last time Prime Minister Scott Morrison announced a shake-up of the top levels of the bureaucracy, the number of major departments and secretarial positions was reduced, and gender parity on the secretaries board was lost.

Secretary of the Department of Prime Minister and Cabinet Phil Gaetjens responded to reports that he would be retiring soon at Senate estimates last week.

"I would put that as fake news at the moment," he said, but didn't rule out retiring soon.

"Who knows what might happen in a week's time or a month's time that I have no control over?" he said.

Professor Murphy paid tribute to Ms Edwards' service on Friday.

"I also want to acknowledge the great contribution that my dear friend Caroline Edwards has made to basically saving the nation over the last 18 months," Professor Murphy said.

Health Minister Greg Hunt said Ms Edwards "has been one of the great servants of the nation".

"She is retiring and I am desperately sad about that but in the darkest of days, last year, she and others were working 20 hours, sometimes 24 hours and the gruelling pace is just incredible," Mr Hunt said.

IN OTHER NEWS:

Before serving as acting secretary and then as associate secretary when Professor Murphy moved into the top job, Ms Edwards served as deputy secretary responsible for social policy at the Department of Prime Minister and Cabinet, and as a deputy secretary at Health and at the Department of Human Services.

Mr Morrison announced Lieutenant General John Frewen, who had been leading the Covid-assist operation within Defence, would become head of the National Covid Vaccination Taskforce.

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