Hays Travel is to cut up to 878 jobs out of a total workforce of 4,500 people, the firm has announced.
The travel company said the Government's decision to advise against non-essential travel and reimpose quarantine requirements for holidays to Spain "triggered the cancellation of hundreds of thousands of holidays".
Hays Travel owners John and Irene Hays said: "We are devastated that after all of our efforts and the huge investment we've made we now face losing some of our valued employees, through no fault of their own.
"Following the decision to ban travel to Spain and the changes in furlough conditions coming at the same time, we have had no choice.
"We are also devastated for everyone who may lose their job and we will do all we can in consultations to help them, as we focus on retaining as many people as possible and rebuilding consumer confidence through our renowned friendly and knowledgeable customer service."
Hays surprised many in October 2019 when it said it was taking charge of all of Thomas Cook's 555 travel agents across the UK, after the 178-year-old firm went out of business.
This prevented thousands of staff from losing their jobs.
Hays said it has had "no significant redundancies in its 40-year existence".
It is consulting with 344 employees who are training as travel consultants and 534 who work in its foreign exchange division.
At the end of last week Mr Hays hit out at the Government's imposition of quarantine on holidaymakers returning from Spain, which he said had destroyed a recovery in the travel sector.
His firm had recovered to around half of last year's tradition levels before the move but has had seen demand drop again, as well as having to contact tens of thousands of customers to help them with new arrangements.
The job losses at Hays follow a similar announcement from travel agent Tui, which is proposing 166 branch closures and the loss of around 600 jobs.
