Drugs and alcohol will be a focus for police this Easter as they mount a statewide operation on the roads.

Operation Nexus runs from 12.01am on Thursday March 28 to 11.59pm on Monday April 1.

Victoria Police is warning motorists that officers could be anywhere at any time.

Major arterials and roads leading to regional Victoria and holiday hotspots will be key areas of enforcement.

The effort will include marked and unmarked vehicles as well as the force’s booze and drug bus fleet.

The state's road toll is currently at 67, and police said deaths on rural roads represent more than half of this year's fatalities.

In addition to impairment, speed, fatigue, distraction and seatbelt compliance will be in the sights of police.

The force’s anywhere, anytime enforcement approach will continue over the high-risk period.

“It’s important to remember every police car is a booze bus and drivers can be breath tested at any time," said Assistant Commissioner Road Policing, Glenn Weir.

“We want everyone to survive this Easter and will be doing all we can to make sure that happens.”

Police intelligence shows a recent a spike in drivers getting behind the wheel when they’re drug or alcohol affected.

During a two-night police operation on the Monash Freeway in February one in 95 drivers tested had drugs or illegal levels of alcohol in their system.

The average usually sits at around one in 400. 

Similarly a two-night operation on EastLink this month saw one in every 148 drivers tested returning a positive drug or illegal alcohol reading.

 A total 13 lives have been lost over Easter in the last six years.