Hundreds of rowdy protesters rallied in Melbourne's CBD on Thursday night in opposition to Victoria's sixth coronavirus lockdown.

The demonstrators, some carrying placards and most not wearing masks, gathered at Flinders Street and moved into Swanston Street as police tried to disperse them.

The large crowd marched through the city chanting "Sack Dan Andrews" and "No more lockdown", while two officers pepper-sprayed protesters when mob members approached them.

A police sergeant suffered minor cuts and abrasions after he was pushed to the ground and kicked outside Melbourne East police station.

"I have to say kicking a police officer while he is down is a dog act," Assistant Commissioner Luke Cornelius told reporters on Friday.

A police car also had its wing mirrors removed and a flare was lit, with images set to be released later on Friday to identify those involved.

Fifteen people were arrested and 16 others fined for various health directions breaches.

Four of those arrested or fined were known protest organisers and are expected to face court on charges such as incitement.

Mr Cornelius said the crowd was a similar mix to those who rallied in Melbourne on July 24, describing it as a small minority of "serial protesters" putting Victorian lives and livelihoods at risk.

"It was certainly volatile last night," he said.

"Of course there were concerned mums and dads, business owners who are very concerned about how the lockout is impacting their lives, how lockdowns impacted businesses.

"But there is absolutely a hardcore element of people who see this as an opportunity to pick a fight with police."

Some of the protesters, he added, were looking to leverage the lockdown to advance their "strange notions".

"There are wolves in sheep's clothing here," Mr Cornelius said.

"There are people who are dressing themselves up as advocates for mums and dads and business owners who are really doing it hard."

Police are not anticipating further protests over the weekend but have vowed to redirect officers should any arise.

The seven-day, statewide lockdown began at 8pm on Thursday, with all public protests outlawed under stay-at-home restrictions.

"All it will do is lengthen the lockdown," Health Minister Martin Foley said.

Australian Associated Press