The importance and topicality of the subject matter under scientific research is determined by the need to carry out an analysis of the emergence process of the buffer-state geopolitical status of the Republic of Moldova in terms of ensuring/ non-ensuring the national security during the global health crisis caused by the COVID-19 pandemic that contributes to the enhancement of the current risks and threats, but also to the emergence of some new challenges to the political component of the national security of the Republic of Moldova. The geopolitical architecture of the regional security environment in the South-Eastern Europe puts pressure on the permanent neutrality status of the Republic of Moldova and gives shape to the two geopolitical scenarios: to preserve the geopolitical status of permanent neutrality with a low level of ensuring national security and defence or to leave the collision area between the great powers and to join the North-Atlantic Alliance, thus ensuring its security and defence on its entire territory recognized by the international community. Investigating the matter of the geopolitical status of the Republic of Moldova during the COVID-19 global pandemic, which triggered the decrease of the level of stability in the security area, brings out the low geopolitical potential of the Republic of Moldova that defines the insufficient level of the institutional capacity of the national defence and security system to ensure territorial integrity that is jeopardised by the geopolitical conflict in the Eastern districts (rayons), whose settlement or conservation process perpetuation can only be achieved through geopolitical talks between the great powers concerning the reconfiguration of the spheres of influence and the ensuring of a sustainable regional security.