Wildlife officials have closed off an area southeast of Fort Resolution after 14 bison carcasses were found in the region in the past week.
Preliminary tests show two of the animals found in the Slave River Lowlands, 80 kilometres from Resolution, died from anthrax.
The majority of the bison were mature bulls.
While those tests have not yet been confirmed by the Canadian Food Inspection Agency, the Department of Environment and Natural Resources has barred travel into the region.
Anthrax occurs naturally in the area.
"Under certain conditions, especially when you have high water conditions followed by hot, dry weather, the spores become concentrated in low-lying areas," said Environment Department spokespersonJudy McLinton.
"The bison then usually contract the disease when they inhale contaminated soil when they're rolling around, wallowing in dust baths."
There have been 12 outbreaks of anthrax in the area since 1962. In the summer of 2000 an outbreak killed at least 42 bison in nearby Wood Buffalo National Park.
McLinton says this is considered to be an average-sized outbreak.
Infected bison cannot pass the disease on to other bison, but humans can be at risk if they come in contact with infected animals or carcasses.
McLinton says the bison carcasses will be destroyed later this week, and the department will conduct flights over the area until mid-August to look for more dead animals.