A mother, a father and their baby daughter died in the single-vehicle accident near Shanks Road, about 30 kilometres west of Casterton, when the four-wheel-drive collided with a large gum tree on a slight bend.

It is expected that fatigue will be the focus of Victoria Police major collision investigation unit detectives, as the family were returning to South Australia after being in Melbourne.

Witnesses at the accident scene said there were no skid marks before the Kia impacted with the tree.

Sergeant Scott Williams, of the Hamilton police highway patrol unit, said a delivery driver came across the accident scene at 7.10am Sunday.

He said police understood that members of the family, originally from The Congo in Africa, talked to people in Hamilton between 1am and 3am on Sunday.

"We're calling for witnesses who may have seen that vehicle as we try to build a timeline of where that vehicle was prior to the accident," he said.

"There's up to four hours where we are trying to determine where they have been and what they were doing."

Sergeant Williams said it could be that the accident happened some time before the four-wheel-drive was discovered by the delivery driver.

"It's a grey Kia Sorento four-wheel-drive," he said.

"Anyone with information is requested to contact the Hamilton police station, Crime Stoppers on 1800 333 000 or the Victoria Police major collision investigation unit at Brunswick."

Sergeant Williams said there were two surviving members of the family - a nine-year-old boy and three-year-old girl.

He said the boy had suffered head and internal injuries but was expected to recover.

The girl received minor injuries as she was in the left-hand rear passenger seat.

Both the boy and girl have been listed as being in a stable condition in the Royal Children's Hospital.