The solo-vehicle crash was reported around 4:40 a.m. on southbound Highway 880 just north of Hegenberger Road, according to the CHP.
A 1995 Mazda was traveling south when a physical altercation apparently occurred between the man and his female passenger. The altercation may have caused the man to lose control of the car, and it crashed into the center divider of the highway, CHP Officer Sam Morgan said.
The man got out of the car and, for an unknown reason, ran to the right hand shoulder of the highway. As he was running back to the center divider, he was struck by a vehicle, Morgan said.
The man was pronounced dead at the scene, and appears to have been hit by other vehicles, including one that did not stop after striking him, Morgan said.
He said investigators do not have any information about the car that did not stop, and that the driver, if found, may not be in trouble.
"Perhaps they're not sure what they struck," he said. "It's not uncommon for someone maybe to not realize they hit a human being."
CHP investigators are contacting all witnesses in the area at the time to try to get information about the vehicle, Morgan said.
The woman who was in the Mazda suffered a broken leg in the initial crash, he said.
The names of both victims are not yet being released, Morgan said.