The Coastguard personnels' vehicle hit the landmine in the Kaldan area of Gwadar, where the multi-billion dollars China-Pakistan Economic Corridor would end.
Five personnel were seriously injured in the explosion near the Iran border and two of them later died in the hospital, a security official said.
The vehicle in which the coastguard were travelling was badly damaged in the blast.
The security forces launched search operation in the areas after the explosion but no arrests had been made.
The separatists want greater control over the resources which are in abundance in the province.
The strategically important Gwadar port is being developed under the ambitious USD 46 billion China-Pakistan Economic Corridor.
The project would link China's western city of Kashgar to the Pakistani port of Gwadar on the Arabian Sea.
The project would pass through PoK and has been strongly opposed by India.
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