The crash happened about 2:05 a.m. on La Jolla Parkway and the vehicle landed about 100 feet west of the interchange with Interstate 5 and Route 52, according to San Diego police Sgt. Bob Dare.
The man was thrown from the vehicle and died at the scene, said San Diego police Sgt. Art Campa. His name was not released pending notification of his family.
Two male passengers were taken to a local hospital with minor injuries, Campa said.
Investigators were still working to determine exactly how the crash occurred, but the vehicle was traveling at a high rate of speed and there is at least one very sharp turn on the roadway just before the scene of the accident, said Campa.