The university students, who were reportedly on their way to their last day of nursing clinical rotations, died yesterday after a tractor-trailer truck failed to stop when traffic slowed, police told local media.
The accident occurred near the city of Savannah, said Brooks Keel, president of Georgia Southern University.
"The loss of any student, especially in a tragic way, is particularly painful. Losing five students is almost incomprehensible," he said in a statement.
Four of the students, who were traveling in two vehicles, died at the scene. Three were taken to the hospital, where the fifth died.
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Two tractor-trailers and five passenger vehicles were involved in the incident, which happened just before 6 am (1000 GMT), local media said.
The accident occurred after a tractor trailer failed to stop, crashing into an SUV then rolling over a sedan that burst into flames, the Atlanta Journal Constitution reported.
Georgia Southern University flew flags at half-staff Thursday and was planning a memorial ceremony in honor of the students.