The incident occurred when the Kerala State Road Transport Corporation bus went out of control while trying to avoid colliding with a motorcycle and overturned after ramming into the car, police said.
Out of the deceased, three were travelling in the car and another was a passenger in the bus, they said.
The deceased were identified as Anish Abraham, his wife Bibina and neighbour Abraham Cherian who were coming from the airport at Nedumbassery near Kochi.
Two car occupants and around 25 bus passengers were injured in the mishap, police said.