The crash happened around 1:30 a.m. at the Carmenita Road exit, according to the California Highway Patrol.
CHP Sgt. Florentino Olivera said a Honda crashed into a big rig that was pulled over on the side of the freeway, killing two passengers inside the car.
The driver of the Honda was taken to the hospital in unknown condition and was arrested on suspicion of driving under the influence.
All but one lane of the southbound side of the freeway was shut down for the majority of the morning. By 9:30 a.m., four lanes had reopened.