A teenager and a man have died and three people have sustained serious injuries in a single-vehicle crash in the state's Orana region on Saturday.
All five occupants were trapped in the wreckage and had to be cut free from the vehicle, the Westpac Rescue Helicopter Service reported.
Three rescue helicopters with critical care medical teams on board along with paramedics, police and emergency rescue services attended the scene at Merrygoen near Mendooran mid-Saturday afternoon.
Police are investigating the double fatality, which happened about 80 kilometres north-east of Dubbo.
The front-seat passenger, a 14-year-old boy, and a 25-year-old man, who was in the back seat, died at the scene, NSW Police said in a statement.
Police confirmed the 25-year-old man was from Gulgong, while the other occupants were all from Menah.
Emergency services were called to the Castlereagh Highway at Merrygoen, about 10km east of Mendooran, at 3.20pm on Saturday after a 2005-model Mitsubishi 380 sedan travelling west left the road and hit a tree.
The driver and four passengers were trapped in the vehicle and had to be released by emergency services, police said.
The driver, a 37-year-old woman, was airlifted to Westmead Hospital with arm fractures.
A 13-year-old boy was airlifted to The Children's Hospital at Westmead with multiple leg injuries, and a 17-year-old girl was airlifted to John Hunter Hospital also suffering leg fractures.
Officers from the Crash Investigation Unit are investigating the circumstances surrounding the crash.
The Westpac Rescue Helicopter Service reported on Saturday night occupants had been airlifted by two helicopters to Westmead and Westmead Children's Hospital, and the Westpac Rescue Helicopter was airlifting a 16-year-old female to John Hunter Hospital with multiple injuries in a critical condition arriving at 8pm.
The crash closed the Castlereagh Highway between Gilgandra and Dunedoo in both directions for some time.