A second child has died in hospital following a single-vehicle crash west of Melbourne on Tuesday afternoon.

A seven-year-old girl died at the scene after a 4WD with seven children inside rolled near Parwan just before 4pm.

An 11-year-old boy was flown to hospital with critical injuries but died overnight.

Five other children were taken to hospital with non-life threatening injuries and the driver, a 34-year-old woman, was taken to hospital for observation.

Detectives are continuing to investigate the circumstance behind the crash, which happened near the intersection of Nerowie and Parwan-Exford roads.

Detective Sergeant Tony Gentile from the Major Collision Investigation Unit said the woman had picked the children up from school.

"From my understanding, the scene was quite hectic, people everywhere, witnesses who witnessed it, they stopped and rendered assistance," he said.

"Obviously, with seven children, they were distressed and they were cared for by paramedics, members of the public and police.

"This is just a really sad set of circumstances, very sad. We just ask the public to drive to the conditions and be mindful of their surrounds."

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