Liberty Insurance is to shed 285 jobs at offices on both sides of the border, including Enniskillen.
The company, formerly Quinn Insurance, expects to cut 70 positions in Enniskillen along with 140 in Dublin and 75 in Cavan.
There are currently around 500 employees in each of the affected offices.
Patrick O'Brien, chief executive of Liberty Insurance, said the redundancies are necessary a year after acquiring the business to protect the remaining 1,100 jobs.
"We are fully committed to the Irish business, will continue to invest in our business, and believe that our arrival has been positive for the Irish insurance market and consumers," he said.
Staff were informed of the developments on Thursday ahead of a 30-day consultation period.
Supporters of the Quinn family, who have staged several rallies in their hometown of Ballyconnell, Co Cavan, claimed the job losses came as little surprise after the family's plan to save the business was rejected.
Adrian McCaffrey, of Concerned Irish Businesses, said: "It is devastating for the employees concerned and their families, especially coming up to Christmas; however, it has been expected for some time now.
"The company formally known as Quinn Insurance has been in decline since the appointment of the administrators some two and half years ago, an appointment which has to date not been fully explained by the Financial Regulator.
"These job losses come at a time of severe social and economic turbulence in Ireland, a time when families in rural Ireland and particularly those in the border region are struggling to survive and maintain any form of community."