The driver may have been going the wrong way for miles before colliding head on with a pick-up truck, killing two people, according to California Highway Patrol.
CHP says a Prius was traveling south in northbound lanes when it hit the truck near Clarendon Road around 4:15 a.m.
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It is unknown where the Prius driver entered highway, but officers say it was likely closer to Interstate 280.
Both passengers in the Prius were killed. They have been identified as one man and one woman, both between 20-30 years old.
The driver of the Prius, identified as a man between 20-30 years old, survived but was taken to the hospital with critical Injuries.
"Unfortunately two passengers in the Prius died on scene, the driver transported to the hospital," said CHP Sgt. David Fawson.
The Prius driver was listed in critical condition at Zuckerberg San Francisco General Hospital. The CHP says the driver and one of the passengers were not wearing a seat belt.
The driver of the pick-up and his passenger were injured and taken to the hospital, both were expected to survive.
CHP says their investigation is still underway, and it's unknown if drugs or alcohol were involved at this time.
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Pacifica neighbor Elonia Butler isn't surprised someone may have accidentally got on Highway 1 the wrong way.
"As you know, those 'do not enter' signs are not lit up at night, people do not understand, if you're not from around here, it could be bad," Butler said.
CHP says there is no evidence the Prius driver was working for Uber or Lyft
This is the second wrong-way incident that ended with a fatality this week in the Bay Area.
Last Sunday, a suspected wrong-way driver on Hwy 101 took the life of Waheed Etimad, a father of seven from Concord. Etimad was an Uber driver, his passengers were injured. The wrong way driver was also killed.