It happened at 7:30 a.m. Friday on Kennett Pike at Stone Brook Drive.
Police say two SUVs collided head-on, trapping two people in one of the vehicles.
At least three people were taken to area hospitals, including a female victim who was airlifted to Christiana Hospital.
Two of the victims were said to be in critical condition.
Kennett Pike was shut down in both directions as police investigated and crews worked to clear the scene.
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