Topshop and Topman stores in Suffolk town centres could disappear after preferred bidder ASOS said there would be no need for high street shops.
The news came on the same day it was revealed that Debenhams stores would not reopen, after new owner BooHoo said it was buying the Debenhams brand - but not its physical shops.
Online retailer ASOS is lining up to buy Sir Phillip Green's Arcadia group, which collapsed at the end of last year.
Topshop and Topman have stores in the Sailmakers Shopping Centre in Ipswich and in The Arc at Bury St Edmunds. They also have two stores in the heart of Colchester.
None are expected to reopen at the end of the lockdown. Across the UK, the closure of Topshop's stores are expected to result in 13,000 job losses.
Two other Arcadia brands left Ipswich town centre a year ago - Burton and Dorothy Perkins.
However, their store was replaced by a new Deichmann shoe shop which attracted customers in the run-up to Christmas, before being forced to close for the lockdown.
Ipswich Central chief executive Paul Clement said the closures would be devastating for the town centre.
However, he said it showed the importance of planning for a future that was not tied to shopping and the need to shrink the town centre as a retail destination.
He said: "This is no surprise, but it confirms what we have been saying, and will continue to say, that we have to look at other things in the town centre like homes and offices - we can't just rely on retail to keep things going."
He added that this is an issue for towns and cities across the country and that it is a long-term trend. He also said the coronavirus crisis has sped up changes that have been coming for a long time.
Mr Clement's opposite number in Bury St Edmunds, Mark Cordell, is also facing up to the possible loss of Topshop - although he pointed out that the final deal had not yet been confirmed.
He added that the chain stores needed support in the town centre, as well as smaller independents.
"There are a lot of people working in stores like Debenhams and Topshop and they need the support of customers as well," Mr Cordell said.
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