The incident was reported just before 9 p.m. Thursday near West 11th Street and the West Side Highway.
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Police say the man went into the water to retrieve property before finding himself in distress. That is when three other people went in after him to rescue him.
Those three people were eventually rescued by FDNY Marine One.
FDNY and NYPD dive crews searched for at least an hour until they found the victim near Pier 45.
The FNDY said just after 10 p.m. that the man was found and taken to Lenox Hill Hospital in cardiac arrest. He was later pronounced dead.
His identity was not yet known.
Few other details were released.
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