Emergency services rushed to the Great Western Highway at Wallerawang, 15km north of Lithgow, following a five-car crash about 12.50pm on Friday.

Police said an Isuzu D-MAX, travelling east and towing a motorcycle trailer, collided with a westbound Toyota HiLux.

The Toyota then struck a Hyundai Tuscan, causing it to leave the road and trapping the occupants.

Meanwhile the Isuzu struck a Kia Carnival head on, and a fifth car, a Nissan Patrol travelling behind the Isuzu, struck the motorcycle trailer.

The 42-year-old male driver of the Isuzu, and the 49-year-old man behind the wheel of the Kia were trapped and died at the scene.

Twenty-one people were treated for varying injuries, including a 41-year-old woman and five children – aged between five and 15 – who were travelling in the Kia.

All six were taken to hospital where one child remains in a critical but stable condition. The other four children remain stable and the woman has since been released.

The 55-year-old male driver of the Hyundai and his two passengers also remain in stable conditions, while the 39-year-old and 42-year-old drivers of the Toyota and Nissan were taken to hospital for mandatory testing.

Addressing the media on Friday evening, NSW Police Detective Superintendent Paul Glinn said it appeared one of the vehicles involved veered onto the wrong side of the highway.

“It would appear that a vehicle has crossed to the incorrect side of the road, but as to the actual circumstances as to what led up to that event and the collision that occurred and what flowed thereafter will be determined in coming days,” he said, describing it as a “significant scene.”

Detective Superintendent Glinn said drivers need to slow down over the busy holiday period.

“There’s a lot of people that are on holidays, a lot of people travelling on roads,” he said.

“Drive to the conditions, slow down. Every time you get behind the wheel you need to make good decisions, and ultimately your responsible for what occurs to ensure the safety of yourself and your passengers.”

Local NSW state MP and opposition roads spokesman Paul Toole told the ABC the community is “hurting” following the crash.

“It’s shocking news and everyone is sending their condolences to those families and loved ones that have been involved in that serious accident,” he said.

“It has a far-rippling effect in our local communities.

“I know the police have not identified those that have been involved in the incident, but we know it is going to cause a lot of heartache and loss.”

Meanwhile, Blue Mountains Mayor Mark Greenhill is urging drivers to be careful on the roads.

“Two people have died in an horrific crash outside of Lithgow,” he wrote on Facebook.

“At this time of year, and in tourist areas like ours, there can be some frustration on the roads with sporadic traffic and people not necessarily knowing where they are going.

“Please drive at or below the speed limit and take it easy. We want people home and safe at the end of the summer break.”

Police are examining the crime scene and are continuing an investigation into the circumstances surrounding the crash.

A report will be prepared for the Coroner.

In 2023 so far, 349 people have died on NSW roads — 70 more than at the same time last year.