A stolen car left an overpass and plummeted onto an expressway south of Adelaide after being involved in a police chase.

A spokeswoman for SA Police said the circumstances of Saturday's crash were still being investigated but confirmed the car came off O'Sullivan's Beach Road overpass at Lonsdale before crashing onto the Southern Expressway.

The male driver of the car was taken to Flinders Medical Centre in a serious condition.

"Just after 2:30pm police sighted a stolen Holden station wagon travelling east along on O'Sullivan Beach Road," SA Police said in a statement.

"Police initially pursued the car but terminated due to safety reasons.

"A short time after the pursuit was terminated, that same car was involved in a serious crash on the Southern Expressway.

"Police and other emergency services responded and assisted the driver who was the sole occupant of the car."

A section of the Southern Expressway was closed for several hours overnight, but has since reopened.

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