The victims include an adult man, two adult women and a baby. A second child sustained slight injuries.
The vehicle that they were travelling in crashed into a car that had careered across the central reservation. The driver of the car that caused the crash has been detained and tested over the legal drink drive limit.
Police commissioner Michaël Vanden Heede: "A vehicle that was coming from the Ghent Kortrijk motorway that crossed the central reservation crashed head-on into the victims' car. It was a head-on crash involving the car in which the five victims were seated."
"The death toll is high: three adults and a baby. A second child aged around 5 was taken to hospital for treatment but isn't seriously injured."