Jim Roddy, manager of Derry’s City Centre Initiative, said the sector “is being driven into the ground”.
If businesses were told to close they would be entitled to financial support.
But while they are allowed to remain open there is no such help.
Mr Roddy called for Stormont to approve financial support for the sector and said without intervention jobs and businesses would be lost.
Speaking on BBC Radio Foyle, Mr Roddy said lockdown restrictions in the Derry City and Strabane District Council area – which came into effect earlier than the rest of the North of Ireland – had reduced footfall so much that businesses allowed to remain open could not trade.
Pubs and restaurants can only open for takeaway, while hairdressers and beauty parlours must close, but non-essential retailers can stay open.
“The indirect result of restrictions being placed on all these other sectors is driving city centre retail into the ground,” Mr Roddy said.
“The net result of that is that people will lose their jobs, these shops will shut up.”
With a hinterland that straddles the Irish border, restrictions now in force in the Republic of Ireland further compound the situation in Derry, he said.
The state’s new restrictions mean people cannot travel more than 5km from home, drastically reducing the number of shoppers who can travel into Derry from neighbouring County Donegal.
“We are facing a major, major crisis. I do not say that lightly,” Mr Roddy said.
“I support our executive ministers in all that they do to try to look after the health and wellbeing of our citizens. But in this instance, our city centre is facing a real crisis”.
Retailers, he said, want to know “how are we meant to stay open in a ghost town?”.
Economy Minister Diane Dodds is due to put forward financial support proposals for traders hit by the Covid-19 restrictions later on Thursday.
Mr Roddy said that must include support for retailers.
“We are in a zone where all businesses have not been paced on restrictions and some businesses cant get special grant aid at this time,” he said.
“Those businesses are really facing the wall and something needs to be done to help them now.”