Police have urged drivers to take more care on the roads, with another death taking the state's "tragic" toll to five in just four days.
The warning comes after two deaths within hours on Tuesday. A female passenger died after the driver lost control of a car in Lima South, north of Mansfield, about noon. Police believe the sedan left the road and hit a tree in a ditch.
Just before 11pm, a man died when he lost control of his Holden Commodore on the Murray Valley Highway at Piangil, north-west of Swan Hill. The man was the only person in the car.
Police say in the other three deaths since Saturday, drivers either lost control or veered from the road and hit a tree or drove into oncoming traffic.
On Monday, a Sunbury woman, 34, died when her car ran off the road on the Calder Freeway near Sunbury.
On Sunday, a Launching Place man, 20, died when his car veered on to the wrong side of the Warburton Highway in Seville East and hit another car.
And on Saturday morning, a man aged in his late teens died when his car left the road and hit a tree on the Princes Highway at Port Fairy.
Assistant Commissioner Bob Hill said drivers needed to take care while driving, particularly on country roads and while on long journeys.
"Don't allow yourself to get distracted, and if you are feeling fatigued, stop and rest," he said.
"I urge motorists to travel at a safe speed, that is, within the limits and the road conditions."