Warrnambool's Midfield Meat will cut 340 job due to strict new coronavirus regulations.
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General manager Dean McKenna said new rules which meant the city's biggest employer would have to operate at two-thirds of its usual capacity would be "disastrous" for the company.
Premier Daniel Andrews announced all abattoirs would have to scale back production on Wednesday.
"We're still going through the data from the state government, (but) in a nutshell it means we've got to put off 340 workers and none of those workers are eligible for job support," Mr McKenna said.
"Midfield can't afford to pay the wages of the 340 workers for six weeks as it relates to a direct cost of $3.8 million. These processes run like a bike chain and you can't run them with missing links."
He said the job losses would have a "dramatic impact" on the region's economy.
"We're in discussions with the state and federal governments as we speak and those talks will undoubtedly continue over the next few days," he said.