The two-vehicle crash took place around 9:45 a.m. on northbound I-95, just south of U.S. Highway 17 when a Ford sedan was moving north on I-95 in the center lane when it made an abrupt lane change and hit the side of a GMC sport utility vehicle traveling in the left lane.
After that, the sedan spun and hit the guardrail in the center median. The SUV stopped on the right side of I-95 North.
An 81-year-old Yulee man who was driving the car was pronounced dead at the scene.
His passenger, a 85-year-old Yulee woman, succumbed to injuries in hospital.
A 77-year-old Dunnellon woman who was driving the SUV and her passenger, a 84-year-old Dunnellon man, were hospitalized over their injuries.
All northbound lanes of I-95 in the area were closed for about two and a half hours but were resumed just after 12:30 p.m.
Florida Highway Patrol was investigating the crash.