Brown Thomas and Arnotts plan to lay off 150 workers - more than one in eight staff members - citing unsustainable losses during the Covid-19 pandemic.
The announcement came just two months after the Weston family-controlled Selfridges Group, owner of both brands, reopened stores here following weeks of lockdown.
Managing Director Donald McDonald, who delivered the news yesterday to staff, called it "the toughest decision I have had to take". He said talks would begin immediately to seek voluntary redundancies following a review of "every function in the business".
Brown Thomas Arnotts said it would consider applications from employees "for career breaks, shorter working hours and early retirement" in a process expected to close by mid-October.
"The retail industry is being severely impacted by unprecedented circumstances related to Covid-19. Brown Thomas Arnotts is no exception. Like many others, we are feeling the effects with sales expected to be significantly down, making 2020 the toughest year we have experienced in recent times," Mr McDonald said.
"And as we face continued uncertainty, with retail unlikely to return to normal for the foreseeable future… we need to ensure our cost base is in line with the level of business we realistically can expect," he said.
Last month, Selfridges in London cut 450 jobs across its four UK stores citing Covid-19 disruption to trade.
Ibec body Retail Ireland said the tough trading conditions at Brown Thomas Arnotts reflected a wider lack of customers in urban centres deprived of tourists, business travellers and office workers.
"While some parts of the sector have bounced back, many retailers remain under enormous stress. City and town-centre businesses are struggling because so many office workers are working from home," said Retail Ireland director Arnold Dillon.
"The trade from foreign tourists has evaporated. Footfall has dropped by as much as 50pc in some areas and the cost base of many businesses is now way out of line with trading reality," Mr Dillon said.
"The focus must remain on protecting viable but vulnerable retailers. This will demand significant additional Government supports," he said.
"The planned VAT reduction is very welcome," he said, referring to the reduced 21pc rate coming into effect on September 1. "Many businesses under pressure will need to use this revenue to protect jobs. The crisis for many retailers is far from over."