Officers and medics responded to the scene, in the 5300 block of 4th Avenue South, at about 2:50 a.m. after receiving a report of a serious collision, said Detective Jeff Kappel of the Seattle police.
A preliminary investigation found that a white 1998 Ford Ranger pickup truck was heading north on 4th Avenue South as a burgundy 1997 Toyota Camry four-door sedan was heading south.
The two vehicles crashed head-on, but the circumstances leading up to the collision are unknown at this time and remain under investigation, Kappel said.
The driver of the Toyota sedan, a man believed to be in his 20s, was pronounced dead at the scene. The driver of the Ford truck was taken to Harborview Medical Center with non-life-threatening injuries.
There were no passengers in the vehicles.