The crash occurred at about 5:30 a.m. on the northbound freeway at Jeffrey Road, the California Highway Patrol reported.
Firefighters and paramedics were dispatched to the location at 5:35 a.m., according to the Orange County Fire Authority, which said it was not immediately known if anyone was taken to a hospital.
No information was immediately available about the fatality.
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The Irvine Police Department reported at 8:30 a.m. that the northbound freeway was closed at Sand Canyon Avenue due to a CHP investigation.