The Grand Ducal Fire and Rescue Corps initially reported that five people had been injured in the collision, which involved two lorries, two vans and a car.
Late on Wednesday night, the authorities confirmed that two men from Germany had suffered fatal injuries in the crash and had since passed away.
The motorway was closed for two hours immediately following the incident, which took place at around 4pm. Three ambulances and five fire fighter teams attended the scene.
The ACL advised drivers to avoid the area, while reports suggested that the tunnel remained closed throughout the night to allow access to the authorities and road safety personnel.
