A man and a woman were in the vehicle that crashed into a Whole Foods truck on the southbound expressway near Heath Avenue, just after midnight.
The occupants were pronounced dead at the scene.
The driver of the tractor trailer was not injured and was being interviewed by police.
Southbound lanes have been closed for hours and traffic is being diverted off at West 230th Street.
Motorists were advised to avoid the area if possible.
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