The two-car crash happened just before 8 p.m. Tuesday on Vista Del Mar near Dockweiler State Beach.
Four juveniles were inside one of the cars. One of them died at the scene and the other died at the hospital. Their exact ages was not known.
The other two juveniles and a woman, believed to be in her 30s, who was in the other car were also taken to the hospital.
Details about what led up to the collision were not available, but witnesses said one of the drivers may have passed out and crashed into oncoming traffic.
Authorities said there was no evidence to indicate one of the drivers was under the influence.