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A car was flattened against a truck in the collision, which happened shortly after 2pm yesterday.
Police confirmed one person died at the scene on State Highway 1 near Lakeside Rd near Crichton.
Senior Sergeant Stan Leishman, of Balclutha, said the single occupant of a northbound maroon Subaru was killed after their car collided with the septic services truck, which was heading south.
The truck driver was not injured in the crash, but was left shaken.
The Septic Tank Services company did not wish to comment on the incident.
The road was blocked in both directions and traffic built up for more than two hours.
Fire and Emergency New Zealand and St John were earlier at the scene.
Members of the serious crash unit later arrived to examine the scene and clear away the wreckage.
A St John spokesman said no-one was transported from the scene.
-By Jack Conroy