The crash took place on the R152 at Keenogue, Duleek shortly after 6.30am.
Emergency services attended the scene where a man (40s), who was the driver and only occupant of a van involved in the incident, was pronounced dead.
A second man (30s), who was the driver and sole occupant of a second vehicle, was taken to Our Lady of Lourdes Hospital where he later died.
No other serious injuries were reported.
The road is currently closed while a technical examiner takes place, with local diversions in place.
Anyone who witnessed the collision, or was driving in the area between 6.20am-6.50am, is asked to contact Gardaí at Ashbourne Garda station on 01-801 0600, the Garda confidential line on 1800-666 111, or any Garda station.