The head-on collision occurred shortly before 8:30 Sunday morning on Kirkwood Highway near Delaware Park Boulevard in Wilmington.
The accident involved a car and SUV. The SUV was traveling at a high rate of speed and overturned upon impact.
The two males inside the SUV both attempted to flee the scene. One male was able to get away, while the other collapsed because of injuries sustained during the accident. Both he and the female occupant of the car were transported to Christiana Hospital where they are listed in serious condition.
Police continue to search for the second male who fled the scene. It is not immediately clear why they attempted to flee.
Kirkwood Highway is closed to traffic eastbound and westbound traffic is getting by on the shoulder.
Delaware State Police continue to investigate.