The train stopped at Parry Sound, Ontario, about 5:30 a.m. and local emergency services personnel confirmed the woman had died, VIA Rail officials said in release posted on the carrier's website.
The other three sick passengers were transported to a hospital for treatment. Their conditions were not provided by VIA Rail.
The medical emergency resulted in 6-hour delay in the train's arrival in Toronto.
VIA Rail, Canada's national passenger rail service, said two rooms the four passengers were occupying on the train were quarantined, a standard procedure in such cases.