The three-car collision was reported just after 1:20 a.m. on southbound Highway 680 at the Crow Canyon Road off-ramp, according to the CHP.
One of the vehicles involved started leaking gas after the crash and one car caught fire. Multiple passengers appeared to be trapped in the vehicle that caught fire, according to the CHP.
Two people were declared dead at the scene, and a third was taken to a hospital with major injuries, CHP Officer James Evans said.
The CHP issued a Sig-alert at 1:36 a.m. and shut down the roadway until about 8:05 a.m., the CHP said.
The crash remains under investigation.