The planned closure of Debenhams in Londonderry has been described as "the darkest hour" facing retail in the city centre.
The firm employs hundreds of people across five stores in NI, with one store being an anchor tenant in the Foyleside Shopping Centre.
It is expected 12,000 staff will lose their jobs UK-wide after the failure of efforts to save the retailer.
Retail NI chief Glynn Roberts said the store was a "huge driver" of footfall.
Staff were told on Tuesday morning about the former high street giant's fate.
The closure of Debenhams on the heels of the Arcadia Group collapse will impact hundreds of employees in stores located in Belfast, Ballymena, Craigavon, Newry and Derry.
Speaking to BBC Radio Foyle, Mr Roberts said: "It's probably the grimmest couple of days we have had in the retail sector in a long, long time."
"This [closure] will do huge and systemic change and damage to our high streets and what we need to focus on is how can we move this forward.
"My real fear is that we will now see a domino effect of retailer after retailer closing and that process will be extremely hard to reverse."
Town and city centres will need to be "reimagined" post-pandemic to become places not just for retail but also for socialising, culture, health, creativity and learning, Mr Roberts said.
'Radical action is needed'
Declan Hassan, a former director of Austin's department store in the city centre, which closed in 2016, said trading on the high street for bricks and mortar businesses has become a "very, very tough game".
He said the recent high-profile casualty in the retail sector means the city centre is facing into its "darkest hour" and is proof that "radical action is needed" to help save town centres.
"The closure of Arcadia and Debenhams is a great tragedy, this is going to cause major issues for the survival of many town centres across the UK and Ireland.
"If there is no initiative to try and save the town centre now, then in five years time it will be in much worse state.
"You cannot see which way it can go in its present form apart from south," Mr Hassan added.
Paul Clancy, who is chief executive of the Londonderry Chamber of Commerce, said "Foyleside is in shock" over the recent news.
Mr Clancy said management in the shopping centre are "hopeful someone will step in to help fill the units left behind by the Arcadia Group and Debenhams" and "will try and keep as many jobs as possible".
Mr Clancy estimated there are now 100 people "who are really struggling over what future they will have" so close to Christmas.
Trade unions have urged for a recovery plan for the sector, which faces the loss of tens of thousands more jobs.
The Union of Shop, Distributive and Allied Workers said staff should be treated with "fairness and dignity".
General secretary Paddy Lillis added: "Each one of those job losses is a personal tragedy for the individual worker and store closures are scarring our high streets and communities."