Deputy Premier James Merlino, Health Minister Martin Foley, Sports Minister Martin Pakula and Police Minister Lisa Neville are all set to announce they will not recontest their seats, according to multiple media reports.
An announcement could come as early as Friday but a Victorian government official declined to comment.
They would join retiring Planning Minister Richard Wynne, who declared the situation an "opportunity for renewal" and paid tribute to Mr Merlino.
"We have a very, very good crop of ministers coming forward and I look forward to this rejuvenation of our cabinet," he told the Nine Network outside parliament on Thursday evening.
"James has been a wonderful friend, a wonderful minister ... he has a wonderful legacy to celebrate."
Mr Merlino refused to be drawn on "speculation" he is retiring, while Mr Pakula indicated he would likely speak on Friday.
While Mr Pakula's lower house seat of Keysborough has been scrapped as part of an electoral redistribution, he was expected to move to the upper house.
Ms Neville took extended leave last year while battling severe Crohn's disease flare-ups, and shed the emergency services portfolio when she returned to work in August.
Mr Foley, who took over from Jenny Mikakos as health minister following her resignation in September 2020, batted away questions about his future on Wednesday.
He said the state is still "in the middle of a global pandemic" and "we've got one or two things to do".
"I look forward to making a contribution to re-elect the Andrews Labor government via the seat of Albert Park," he told reporters.
If he does resign from cabinet, Victoria would need to appoint its fourth health minister in as many years.
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