The accident occurred on southbound I-95 in the area of Marsh Road in Wilmington at 8:07 p.m.
Police tell Action News a Volkswagen Jetta, driven by Rafael Martinez-Garcia, 25, of Wilmington, went out of control, left the roadway and struck a guardrail several times.
Investigators believe Martinez-Garcia was ejected from the vehicle. He was taken to the hospital in critical condition.
Two other passengers were taken to the hospital with non-life-threatening injuries. One passenger was identified as Raul Ortega-Squivel of Newark, Del. The other passenger's name was not immediately available.
Two other cars were involved in a minor crash as a result. Those drivers were not seriously hurt.
The investigation caused the closure of the southbound lanes of I-95 for five hours.
An investigation into this crash continues.