The deputies were responding with lights and sirens to the scene of another accident at around 10 p.m. Wednesday when their cruiser collided with a Chevrolet pickup truck.
The accident happened at the intersection of Temple Avenue and Valley Boulevard in Pomona.
Rescuers used the Jaws of Life to extricate the victims from the mangled vehicles. The two deputies were airlifted to Los Angeles County-USC Medical Center. One other person was seriously hurt.
The cause of the crash is under investigation.