The explosion on Saturday struck an armoured vehicle carrying the soldiers to a remote base near Gumbad, some 75km north of Kandahar, broadcaster CTV said.
Three soldiers were killed at the scene. A fourth was flown to Kandahar and died in hospital, the Canadian broadcaster reported.
In February, Canada took over command of an international force charged with hunting down the fundamentalist Taliban militia in southern Afghanistan. Ottawa has some 2,300 troops in the region.
Militants loyal to the Taliban regime toppled by a US-led offensive in late 2001 are still carrying out attacks on foreign and Afghan targets, mostly in the south and southeast.
Since 2002, 15 Canadian soldiers have been killed in Afghanistan. A Canadian diplomat was also killed in a car bomb attack earlier this year.