Emergency services were alerted to the fire in a house at Deerpark, on the outskirts of Swinford, at around 2am.
It's understood the fire had spread extensively through the property and several units of the Mayo Fire Service spent a number of hours bringing it under control. A local retired couple, who were well known in the area, having operated a business in the town for many years, died in the fire.
Gardaí and the fire service remain at the scene which has been preserved for a technical examination. The examination will seek to determine the exact cause of the fire.
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