The head-on collision on the southbound Santa Ana Freeway was reported around 3:10 a.m., according to the California Highway Patrol (CHP).
A Toyota Yaris that was traveling north in the southbound lanes collided with a Nissan Sentra, said CHP Officer C. Latshar.
The wrong-way driver, a 27-year-old man, was killed.
A 20-year-old woman who was driving the Nissan and a 20-year-old woman who was riding in the backseat also died in the crash, the CHP reported.
Their names were withheld, pending notification of relatives.
Two men, ages 18 and 19, were also riding in the Nissan -- one in front and one in back. They were taken to a nearby hospital in critical condition, a Los Angeles County Fire Department dispatcher said.
The southbound lanes were closed while an investigation was conducted and were reopened about 6:40 a.m., according to the CHP.
