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A police spokeswoman said officers were called to the crash at the intersection of Woodburn Rd and SH1 between Maheno and Herbert.
Police earlier said two people were treated for whiplash, but a St John update suggested the patients were more seriously injured than first thought.
St John spokesman Gerard Campbell said two patients were transported to Dunedin Hospital by ambulance, one seriously injured and one with moderate injuries.
It appeared SH1 remained clear after the crash in at least one lane.