The fire broke out just before 8 p.m. in a two-story home on County Road in Manorville.
When firefighters and EMS arrived, both victims were outside the home.
Officers immediately called for two medivac helicopters to airlift the victims to Stony Brook University Hospital's burn unit.
The man suffered burn injuries and is in serious condition. The woman suffered non-life-threatening injuries.
The fire was brought under control in about an hour.
The house sustained heavy damage.
The Suffolk County Arson Squad and Town of Brookhaven Fire Marshal's office are investigating.
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