Fire broke out on the top floor of the four-story apartment building on 162nd Street just after 4:40 a.m. Wednesday.
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The two victims, a 76-year-old woman and 81-year-old man, were found in the fourth floor apartment and pronounced dead.
They appear to have been husband and wife.
Another person was treated at the scene for non-life-threatening injuries.
The fire is not suspicious, and there was a clutter condition in the apartment that may have helped the flames spread.
The cause is under investigation.
The fire was the second of two deadly, early-morning apartment fires in the city in less than two hours.
The first killed a 27-year-old man in Bedford-Stuyvesant, Brooklyn.
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