The crash happened at about 7:46 p.m. near the intersection of Pelican Hill Road and Newport Coast Drive, according to the Newport Beach Police Department.
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The two people killed were in a Nissan when it collided with a Range Rover.
It was unknown if the driver of the Range Rover was injured, or if anyone else was hurt.
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Further information, including what led up to the crash, were not immediately available.
The crash happened right before another deadly collision in Southern California Tuesday. In Pasadena, witnesses say a grandmother was killed in a two-car crash caused by a wrong-way driver.
RELATED: Pasadena car crash caused by wrong-way driver kills grandmother, witnesses say
Pasadena car crash caused by wrong-way driver kills grandmother, witnesses say