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A single vehicle crashed in Old Coach Rd, near Gore, about 2.30pm.
A police spokesman said one of the occupants died at the scene and another was flown to hospital in a serious condition.
The road was closed for a time and the Serious Crash Unit was investigating the cause.
Soon after, about 3pm, a bus with schoolchildren on board crashed into a parked vehicle in Invercargill.
A St John spokesman said there were 59 people on the bus and one person was taken to Southland Hospital with minor injuries.
A reporter at the scene said the bus windscreen was almost entirely caved in, while another vehicle had been pushed on to the footpath and into a stone fence.
Donovan Primary School Board of Trustees chairwoman Jill Wilkinson said the children were picked up by another bus and taken back to the school.