The incident occurred when five members of a family from Palakkad in the neighbouring state were proceeding to Velankanni in the district, in their car this morning, they said.
When the car approached Velankanni, the driver suddenly noticed a bullock cart in front and swerved to avoid hitting it but collided with a van that came in the opposite direction.
In the impact, three occupants of the car were killed on the spot while two others sustained injuries and were admitted to Nagapattinam government hospital, police said.
The driver of the other vehicle also suffered injuries and has been admitted to the hospital.
A case has been registered investigation is on, they said.