The accident happened in the southbound eastern spur near mile marker 116.
Turnpike spokesman Joe Orlando says the crash apparently started when debris from a tractor-trailer struck vehicles behind it.
When two motorists got out of their cars to check for damage, they were struck by another vehicle.
"This is an accident. Any other day of the week we see them, but this is Christmas eve and it took on a much more devastating feel," Orlando said.
Around 6:40 Friday morning, a wheel came off of a car carrier. That driver pulled over on the side of the road.
But a few yards behind it, the driver of a silver minivan hit the tire and stopped in the middle of the highway.
Then the driver of a white minivan hit the silver one.
Both men were standing on the turnpike when they were hit by a red car. The driver may not have seen them in the early dawn hours.
"It looks he was trying to remove the debris from underneath the vehicle. That's what we're looking at this point," Orlando.
One of the victims was identified as 40-year-old Francisco Martinez of North Bergen. The second victim is from New York City, but authorities have not released his name.
Four other people who suffered injuries in the accident were taken to Hackensack University Medical Center for treatment.
The turnpike's southbound eastern spur was closed for hours during the investigation.