Blowing snow severely reduced visibility on the highway and witnesses said there were near whiteout conditions before the crash.
The Ottawa Paramedic Service was one of three paramedic teams that responded to the crash site and reported that a tractor-trailer was on fire. Firefighters have since extinguished the blaze.
The collision occurred at 4:30 p.m. and police closed the eastbound lanes of the 401.Traffic is being re-routed along old Highway 16.
As of 8 p.m., the eastbound lanes remained closed while some people remained in their damaged vehicles wondering how long they would be there.
Three transport trucks are sandwiched together. One of the trucks appeared to be transporting shredded documents as little bits of paper littered the highway.
Two people were seriously injured and were taken to hospital, but their conditions are unknown. Ottawa paramedics also transferred another two victims to hospital — one suffered a hip and shoulder injury and the other had a broken leg.
Ontario Provincial Police said the 401's eastbound lanes would be closed for an undetermined amount of time while the cause of the pileup is investigated.