It happened just after 3 a.m. at the intersection of Morgan and Blount streets.
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Police said Christian Cosme, 24, was driving a Dodge SUV on Morgan Street and Austin Baucom, 23, was driving a 2004 Acura sedan on Blount Street when the two vehicles collided.
Baucom died at the scene. Cosme suffered serious injuries and was taken to WakeMed, authorities said.
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Police are still investigating. No other information was released.