The crash occurred at about 2:30 a.m. near the Imperial Highway off-ramp, the California Highway Patrol said.
First responders rushed to the scene and worked to rescue multiple people who were trapped in the wreckage.
At least one person died at the scene, authorities said.
The carpool lane and the two left lanes of the northbound freeway reopened around 6 a.m. after crews cleared the area.
No additional information about the victims or the cause of the crash was immediately available.