Store Chief Executive David Thompson blamed the city's $6 billion infrastructure redevelopment, known as the Big Dig, for contributing to the store's $2 million loss.
"They dug up the road outside the store, the buses no longer stopped outside our door and the street became one way," he told The Liverpool Echo.
Customers did not return after the road work was completed, he said.
City officials, who denied the public-works project was to blame for Lewis's problems, pledged to help the store -- one of four remaining Lewis's stores in England -- stay afloat.
The three other stores are profitable, the newspaper said.
The Liverpool store employs 250 people.