The crash happened at 11pm last night on Fairdown Rd, State Highway 67, just outside of the West Coast town.
One person died at the scene.
Police last night expressed disappointment that the speeding crackdown, in which tickets are being issued for speeds of more than 4kmh over the posted limit, had failed to prevent the fatalities.
A head-on car crash in Southland killed one person and seriously injured two children.
The two-car crash in Southland occurred on State Highway 93, about 15km east of Mataura, about noon on Saturday, closing the road for seven hours.
Senior Sergeant Dave Raynes, of Invercargill, said Jessie McKenzie Lineham (20) died at the scene.
She was from Invercargill but studied at the University of Otago in Dunedin.
The 46-year-old driver of the other vehicle received moderate injuries and was taken to Southland Hospital, where he remains in a "satisfactory condition".
His two children, an 8-year-old boy and 11-year-old girl, were flown to Dunedin Hospital, where they underwent surgery for what are believed to be serious injuries.
The cause of the crash was not yet known and police inquiries were continuing.
Witnesses were urged to contact Invercargill police.
The crash was followed by another two-car smash about 4pm on Kaikokopu Rd in Brunswick, 11km north of Wanganui, police said.
One person, believed to be a female passenger, died, raising the weekend road toll to six.
Senior Sergeant Maggie Windle, of Invercargill, told the Otago Daily Times last night it was too soon to say whether speed was a factor in the crash near Mataura, but driver behaviour across Southland had otherwise been "reasonable".
About 30 motorists had been caught speeding on Southland roads - based on the reduced tolerance over the holiday weekend - after more than 1000 motorists were checked by police using speed laser guns, she said.
"People seem to be taking notice and adhering to the road conditions and the rules."
Elsewhere, a truck driver died in a crash near Kaikoura yesterday morning.
The accident happened on State Highway 1 near the Conway River bridge, at 8.30am.
Earlier yesterday, two people died in a crash in north Waikato.
Police suspect alcohol and speed were factors in the crash.
District road policing manager Inspector Leo Tooman said the deaths appeared to "have been preventable".
He said they came as a "bitter blow to our staff trying to maintain a highly visible presence as we work to keep the holiday road toll down".
On Friday, one person died and a second was injured in a head-on collision on State Highway 2 at Matamau, near Norsewood in southern Hawkes Bay, about 8.15pm.
Mr Tooman urged motorists to plan their journeys home and allow plenty of time, taking regular rests and being extra patient in heavy holiday traffic.
The official holiday runs from 4pm Friday until 6am tomorrow.
