The accident happened about 7 p.m. Wednesday near the small community of Gregg, about 50 kilometres east of Brandon.
CN said in a release that the cars were carrying refinery cracking stock, a non-regulated commodity, and that one of them spilled some of its load. A company spokesman said the hydrocarbon product isn't dangerous.
CN said the product did not get into any waterway, but an emergency plan was activated and crews were working with Manitoba environmental officials to clean the ground adjacent to the track.
The company said there were no reports of injuries and there was no threat to public safety.
CN also said the main track was reopened following repairs and investigators were looking for the cause of the derailment.
CN was also involved in a fiery derailment on Saturday just outside Gogama in northern Ontario.
The track and a bridge were destroyed, and a trace of oil product was found in the mouth of the local river system.
There have been three recent CN derailments in northern Ontario, including two along a 40-kilometre stretch of track about an hour south of Timmins.
On Wednesday, the Canadian government proposed tough new standards for rail tank cars used to transport crude oil. The proposal would require the cars to have outer "jackets," a layer of thermal protection, and thicker steel walls.