Two people have been killed in a head-on collision.

Just before 6am on Monday morning, two cars collided at the intersection of Westall Rd and Rosebank Ave in Clayton South, in Melbourne‘s southeast.

WATCH THE VIDEO ABOVE: Victoria road tragedies

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The two drivers, a man and woman believed to be in their 50s, died at the scene.

Police Inspector Graham Higginbotham said it would appear that the woman travelled onto the wrong side of the road.

“It’s indicative that the smaller car has gone across that median strip onto the wrong side of the road,” he said.

He said it was unclear what caused the car to veer onto the other side of the road, but fatigue, a medical episode and speed were all factors that were being considered.

Westall Rd was closed in both directions between Heatherton Rd and Centre Rd but has since reopened.

Impacted buses on routes 705, 824 and 979 are also resuming as normal.

Higginbotham said it was a “shocking” weekend on Victoria’s roads, with six dead over the past 48 hours.

At about 8.20am, a man was critically injured when he was struck by a car in West Footscray.

In a separate incident, a 26-year-old man was found dead in a car in Swan Hill. It’s believed he lost control of his car and crashed.

On Sunday night, a mother was killed and her husband and two children were seriously injured in a horrific collision in Trafalgar in Gippsland.

The driver and passenger of the second vehicle were also hospitalised.

Also on Sunday, a 43-year-old man was killed in a two-vehicle collision at an intersection in Pootilla, east of Ballarat.

At about 4.30pm the same day, a 53-year-old male motorcyclist was killed after colliding with a car in Moutajup in the state’s west.

The motorcyclist’s passenger was airlifted to hospital with life-threatening injuries.

Higginbotham described the events as “tragic”.

“We can’t explain why suddenly this weekend has gone so bad.

“It’s been beautiful weather (and) the roads aren’t saturated.”

Anyone with information about the crashes are urged to contact Crime Stoppers.