Defense Minister Juan Carlos Pinzon said the two suspected members of the Revolutionary Armed Forces of Colombia (FARC) died in an operation to destroy an explosives factory on Saturday in the Vistahermosa region.
The action came three days after Santos ordered the resumption of bombardments against the FARC. That decision followed a FARC attack that killed 11 Colombian soldiers last week.
The continued violence comes even as the Colombian government and the FARC are in peace talks that have been under way in Havana since November 2012 in a bid to end more than five decades of conflict that have killed more than 200,000 people.
Formed in 1964 amid a peasant uprising, the FARC has an estimated 8,000 fighters, deployed in rural areas of the country.