The collision, involving a car and a van, happened on the Ballynahinch Road, on Tuesday morning at approximately 8.15am. A fire started after the collision.
The death of 51-year-old Paddy Bailie from Kircubbin followed the earlier death of a man in his 20s after a crash involving a car and a van on the Ballynahinch Road.
Four other men remain in hospital after the collision. One of the men is described as critical.
Another man is said to be in a stable condition and the other two have injuries which are not believed to be serious.
Station Commander Neil McGrath paid tribute to the rescuers: "Two off-duty firefighters travelling on the road on their way to work were the first people on the scene.
"Watch Commander Stephen Brown, Whitla Fire Station was able to assist three people from the burning van and as he was wearing motorbike protective gear he was also able to act as a barrier between the heat of the fire and the casualty in the car.
"Without his actions we could have been looking at an even more tragic incident.
"Firefighter Paul Cassidy, Cadogan Fire Station was also on the scene and was able to assist the Ambulance Service and the initial attending fire crews."
The Ambulance Service said it had been "a major collision" to which they sent five crews, who were assisted by rapid response paramedics and a doctor.
They said the treatment of the patients at the scene was made more difficult by the fire and that the people in the van suffered burns along with their other injuries.