The man was driving a 1999 Chevrolet Malibu northbound on the freeway, south of Nobel Drive, around 4:20 a.m. when the car drifted off the right side of the road and then swerved back to the left across all lanes, said CHP spokesman Brad Baehr.
The Malibu struck a steel guardrail in the center median, then came to rest facing south across two lanes of the 805, according to Baehr.
Moments later, the Malibu was sideswiped by a 2009 Chevrolet Cobalt just as the man in the Malibu was getting out of his vehicle, Baehr said.
The Malibu was then struck by a 2004 BMZ 325 and a large SUV, the officer said.
The man driving the Malibu was taken to Scripps La Jolla Hospital with major injuries to his legs and possible head trauma, Baehr said.
A 39-year-old San Diego woman who was driving the Cobalt was also taken to Scripps when she complained of chest pain.
A SigAlert for the area was lifted shortly before 7 a.m.
Cal Fire is at the scene of a wildfire burning off State Route 94 near Church Road in the Campo Indian Reservation.
A small plane crashed Saturday evening near the El Capitan Reservoir, the San Diego County Sheriff's Department confirmed.
Backers of an initiative that would allow San Diego State University to buy the SDCCU Stadium site in Mission Valley for campus expansion are scheduled to begin seeking petition signatures Saturday.
Friends and relatives of a couple whose bodies were found in Joshua Tree National Park say they believe the two got lost while hiking in the sprawling desert park and struggled in the searing heat with little food or water before they died in a "sympathetic murder-suicide."
Sunshine and higher temperatures are making the return to San Diego County Saturday after intermittent drizzle across the region on Friday.
President Donald Trump is portraying the Islamic State group's ouster from its Syrian stronghold as a milestone in the U.S. fight against terrorism and a step toward a political transition and lasting peace in Syria.
The San Diego Police Department announced Saturday that officers will step up pedestrian safety enforcement operations.
The San Diego Gulls allowed power-play and shorthanded goals in the first period and an empty-net goal in the third in a 4-2 loss to the Stockton Heat Friday night at Stockton.
Authorities asked the public Friday for help in identifying and tracking down a pair of thieves who have carried out a two-week series of bank robberies this month in the San Diego area.