Three people have died and two are in a critical condition after a crash on the Princes Highway south of Sussex Inlet.
Emergency services were called to the scene 400 metres north of the Bendalong Road turn-off about 10.45am to reports of a head-on collision between two cars, an ambulance spokesman said. One of the cars was towing a caravan.
One of the vehicles burst into flames and three people from two separate cars died.
Paramedics treated two women for multiple serious injuries including possible head injuries, the ambulance spokesman said.
One woman was airlifted to Liverpool Hospital, and the second woman was airlifted to St George Hospital. Both were in a critical condition, police said.
Police closed all lanes of the Princes Highway but had reopened one lane at Bendalong by about 2.30pm.
Motorists are advised to delay travel in the area or to expect significant delays, as traffic is very heavy and moving slowly.
Police warned motorists the highway will remain partially closed for several hours, and urged them to use an alternative route or delay their travels to avoid the area.
Diversions are in place with motorists heading north requested to use the Kings Highway and Braidwood-Nowra Road and southbound traffic to take the Braidwood-Nowra Road and then Kings Highway.
Holiday road death toll double last year's
The triple fatality comes after a horror holiday period on NSW roads.
There were 13 deaths by the end of Christmas Day, and another four by midday on Boxing Day alone, taking the holiday road toll to 17. In the same period last year, there were seven fatalities.
The Operation Safe Arrival road safety campaign runs from Friday December 15 to midnight on Monday January 1.
Now in its 12th day, Assistant Commissioner Michael Corboy, Commander of the Traffic and Highway Patrol Command said the death toll was "appalling".
"That is more than one person a day which is quite alarming. It is just not good enough," he said.
"NSW residents need to take some responsibility and realise that all it takes is one distraction and you could lose your life or kill a family travelling on the roads this holiday period.
"It is a time to be merry and enjoy spending time with your family and unfortunately day after day, police are left to pick up the pieces and deliver horrific messages to families."
Early on Boxing Day there was a fatal single-vehicle incident about 40 kilometres from Port Macquarie.
Emergency services rushed to the scene at Pappinbarra about 6.50am after reports a car hit an embankment. They found the body of a man at the scene. He was yet to be identified.
On Christmas Day, there was a fatal single-vehicle crash near Griffith.
Police believe the male driver of the car left Rankins Springs Road at Beelbangera before hitting a power pole. The male driver is also yet to be identified.
Police have issue thousands of infringement notices during Operation Safe Arrival.
As of Christmas Day, police issued almost 12,400 speeding tickets, charged 710 people with drink-driving and attended 999 major crashes.