Out in Lakeshore, emergency crews were called to a home in the 600-block of Old Tecumseh Rd. just after 2am Saturday.
Two people were transported to hospital with non-life threatening.
The road between Wallace Line and County Rd. 22 was closed for several hours, but has since reopened to traffic.
The Ontario Fire Marshall has been called in to investigate the cause and damage.
OPP are asking anyone with information about the fire to contact police or Crime Stoppers.