Department of Health and Human Services secretary Kym Peake has become the third resignation among key witnesses at Victoria's hotel quarantine inquiry.
She follows Health Minister Jenny Mikakos and the state government's most senior public servant, Department of Premier and Cabinet secretary Chris Eccles, who also quit their roles.
Ms Peake's resignation comes ahead of the inquiry's findings, which are due by December 21.
The inquiry heard Ms Peake received an email on April 9 warning of a "risk to the health and safety of detainees" due to governance issues.
She told the hotel quarantine inquiry she regretted not being able to prevent the second wave of coronavirus.
Ms Peake also failed to brief Ms Mikakos on two Safer Care Victoria reports which identified problems with the hotel quarantine program.
The state's second outbreak resulted in more than 18,000 new infections and 750 deaths.
Professor Euan Wallace will start as the new department secretary from next week.
He is a professor of obstetrics and gynecology at Monash University, and has been on secondment from his role as chief executive at Safer Care Victoria to serve as deputy secretary at the DHHS.
The Victorian government said in a statement that Ms Peake is resigning to pursue other opportunities.
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