The crash happened at around 3am on the northbound carriageway near Junction 3, after a vehicle travelling southbound on the northbound side of the motorway collided with another car.
Gardaí and emergency services were alerted after reports of the vehicle travelling in the wrong direction.
A number of people travelling in the wrong-way vehicle died in the collision, with Gardaí yet to release further details as efforts to establish the identities of those involved continue.
Four people travelling in the second car, including a child, were taken to hospital with serious injuries.
The female driver and front-seat passenger, both aged in their 30s, were brought to Tallaght University Hospital where they remain in critical condition.
A woman aged in her 20s, who was travelling in the rear of the vehicle, was taken to St Luke’s General Hospital in Kilkenny with serious injuries.
A child who was also travelling in the rear of the car was taken to Children's Health Ireland at Crumlin and is in serious condition.
The group is understood to have been travelling towards Dublin Airport when the crash occurred.
Gardaí have appealed to anyone who was on the M9 between 2am and 3am this morning and may have witnessed the incident to come forward.
They are particularly seeking motorists who may have dashcam footage showing the vehicle before the collision.
A Garda spokesperson said: “Gardaí and emergency services were alerted to a vehicle travelling southbound on the northbound carriageway of the M9. The vehicle was driving on the M9 between junction 3 and 4 when a head on collision occurred with a second car.”
The spokesperson added: “A number of fatalities have occurred and no further details are available at this time.”
A forensic collision examination is due to take place as Gardaí work to establish the circumstances surrounding the crash.
The section of the M9 between Junction 3 and Junction 4 remains closed in both directions, with local diversions in place.
Transport Infrastructure Ireland has warned motorists that significant delays are expected in the area and has advised drivers to consider alternative routes.
Fiosrú has also been notified of the collision after the vehicle travelling in the wrong direction had interacted with Gardaí before the crash.
An on-call investigator from Fiosrú attended the scene and an independent investigation is under way.
The organisation said a referral does not necessarily mean that a Garda has been accused of wrongdoing, but that its statutory role is to examine incidents involving contact with Gardaí where someone has died or been seriously injured.
Gardaí are asking anyone with information to contact Athy Garda Station on 01 666 6000, the Garda Confidential Line on 1800 666 111, or any Garda station.
Investigations into the fatal collision are ongoing.
Just last week Gardaí responded to a similar incident of a collision occurring after a stolen vehicle collided with another head on, on the M50 in Dublin.
