Officers were called to the intersection of East 10th and N. Spruce streets around 2:00 a.m. Sunday.
They arrived to find a man in his 20's, on the ground and unresponsive in the 700 block of East 10th.
The man was rushed to Christiana Hospital where he was pronounced dead.
Anyone with information is asked to call Wilmington Police Detective Division at 302-576-3620.