RCMP say the crash happened when the northbound bus collided with a smaller southbound vehicle Tuesday evening on an undivided portion of Highway 63, about 110 kilometres south of Fort McMurray.
The impact killed two males in the second vehicle and left one person on the bus with critical injuries.
A number of other people on the shuttle were treated at hospital for minor injuries.
Police say the 20-seat bus was taking eight passengers to a work camp in the area at the time.
The road was closed for several hours while they investigated.
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