Owner of Wyndham St's The Courtyard Motor Inn Brendan Magee said several guests departed on Thursday to return to Melbourne.
“We're getting cancellations, and requests for confirmation about refunds for pre-paid bookings. We've assured customers they will receive a refund,” Mr Magee said.
He said it had taken weeks to recover from February's snap lockdown.
“Things stopped dead then, and this is exactly the same. It took us three weeks to get going again after that,” he said.
Despite the bad news, Mr Magee and wife Kerry remained philosophical about the new lockdown.
“We're feeling pretty flat at the moment. But it's a necessary thing. The only good thing about it is, it might get people off their backsides to get vaccinated,” Mr Magee said.
Shepparton's Big Valley Motor Inn owner Anthony Lopiccolo described the situation as a "kick in the guts".
“We were really busy after the February lockdown, now we're back to this,” Mr Lopiccolo said.
He said at least two of his guests had already left on Thursday morning to head back to Melbourne.
He believed Australia needed to keep its international borders closed.
“We've got to keep ourselves safe. Let's hope this is over soon, but it hurts,” he said.
Sue Pollock at The Bell Tower Motor Inn on Wyndham St said she had lost three customers who were planning on staying for the weekend, but were now heading home.
She also said since February things had been improving.
“Up to now we've been travelling well,” she said.
She said she had one visitor, a nurse, who was able to stay because she was a frontline worker.
Ms Pollock said February's lockdown was over Valentine's Day and a big athletics weekend in Shepparton.
“We lost two weekends of bookings then. But it's too early to tell what will happen this time - it's the unknown,” she said.
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