The two-vehicle crash occurred just south of Alicia Parkway about 10:55 p.m., Orange County Fire Authority Larry Kurtz said.
TMZ said it has reached out to Ferrell's representatives to get an update.
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Two other victims also suffered minor injuries, while a fourth passenger was transported in critical condition to a local trauma center. The actor and comedian was reportedly speaking on the phone as emergency personnel loaded his stretcher into an ambulance. Another noted: "Hope you are okay, thinking of you and everyone involved in the accident!"
In video footage from TMZ, an upright SUV appeared badly damaged, with the windshield and two windows completely shattered. All three have been taken to hospital. A woman in his vehicle was seen bleeding after the crash, a witness told TMZ.
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The auto flipped and came to a stop on its side in the middle of the freeway, which had to be temporarily shut down, KTLA5 reported.
He was on the way back from a "Funny or Die" event in San Diago.
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"Thoughts and good wishes to Will Ferrell, I hope he's okay".