Two pickup truck drivers died in a 40-vehicle pileup early Thursday on fogged-in Interstate 10, NBC station WDSU reported.
All I-10 eastbound and westbound lanes of traffic were closed nearby, WDSU said.
Police say the 4 a.m. accident sent 22 people to the hospital. Officials said another 37 people refused treatment.
One firefighter also suffered a cuts on his face.
Investigators had not yet released the victims' names, and haven't said what caused the accident.
The wreck caused a miles-long backup on the freeway during the morning rush hour commute, as tow trucks labored to clear the disabled vehicles from the busy stretch of interstate.