Two cars and a B-double truck collided at the intersection of the Murray Valley Highway and Labuan Road in Strathmerton, about 250 kilometres north of Melbourne, about 2.30pm yesterday.
Five people, who are believed to have been travelling in the same car, died.
Three other people, who were travelling in the second car, were taken to Goulburn Valley Health with non-life-threatening injuries.
A woman in her 20s was treated for upper body pain, while a man in his 50s is in hospital with lower body pain.
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A man believed to be in his 20s was taken to hospital for observation.
The truck driver was uninjured and stopped at the scene.
The exact cause of the collision is yet to be determined.
Anyone who witnessed the collision or has dashcam footage is urged to contact police.
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