The accused are also wanted for the attempted murder relating to injuries sustained by a four-year-old girl in the same fire.
Shellbrook RCMP added that a third man, Dominic Chase Ahenakew, 19, had been arrested and charged with two counts of second-degree murder.
Police were called to the fire around 1:30 a.m. CST Monday.
They said the home was engulfed in flames and it was impossible for anyone to get inside to search for victims.
The four-year-old had already been rescued from the burning home and was taken to hospital for treatment of smoke inhalation.
Police identified the men who died as William Ahenakew and Trez Sparvier-Scott. A spokesman for the RCMP told CBC News the victims and the accused were not related.
Canada-wide warrants have been issued for Kimmy Randall Bear, 24, and Carl Anthony Albert, 21. Both men are from the Ahtahkakoop First Nation, which is about 75 kilometres northwest of Prince Albert.
Police were asking anyone with information about where the two may be, to contact them at 306-747-2606.