The incident occurred around 2.30am in Rathowen.
Gardaí are appealing for witnesses following a crash in Westmeath overnight.
Shortly after 2:30am, Gardaí and emergency services responded to reports of a collision involving a car in Rathowen Village.
The two men, both in their 20s, were transported to Tullamore Hospital with serious injuries.
The scene is currently preserved for examination by Garda Forensic Collision Investigators and the N4 at Rathowen Village is currently closed to traffic.
Diversions are in place and will affecting those travelling between Mullingar and Longford.
Motorists are advised to plan their journeys accordingly.
Gardaí are appealing to anyone who may have witnessed this collision to come forward.
Road users who may have camera footage (including dash-cam) and were travelling on the N4 near Rathowen Village at the time of the collision are asked to make this footage available to investigating Gardaí.
Anyone with information is asked to contact Mullingar Garda Station at 044 938 4000, the Garda Confidential Line at 1800 666 111, or any Garda Station.
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