The 49-year-old woman was travelling alone from her Melbourne home to Hamilton when her Hyundai sedan veered off the Glenelg Hwy and collided with a tree at Smythes Creek. She died at the scene.

A passerby discovered the wreckage about 7am but Ballarat police traffic management unit Sergeant Ross Humphrey said it was yet to be ascertained what time the collision occurred.

He said preliminary investigations did not point to alcohol or speed as factors in the crash and said though fatigue had not been established as the cause, all drivers should be well prepared if travelling overnight or through the early hours of the morning.

"If drivers are travelling long distances, they need to take regular breaks away from vehicle and possibly only drive two hours maximum," he said.

"If they are tending to drive longer distances, they need to have had good regular sleep, no manual stress or exercise or work stress just prior to driving."

Sgt Humphrey said extremely fatigued drivers were just as dangerous as drink drivers or speeding motorists on the roads but proved much harder to police.

"If you are sleep deprived, it can amount to driving over the blood alcohol limit," he said.

"Often people think by turning on the air conditioning or the radio or opening a window, that it will help but they don't.

"If you are sleep deprived and fatigued, it won't make a difference and a split second microsleep is all it takes.

"Fatigue appears to be a high contributor in a number of single or multiple vehicle crashes but it's not something you can actually measure.

"It is a funny quantity, because it's one of those things people are aware of and know they shouldn't be doing but they will still drive fatigued."

Sgt Humphrey said people should factor in rest breaks when planning their trips, particularly if driving irregular hours.

"Plan ahead so you can stop, get out of the car and walk around to wake yourself up if you need to," he said.