Over the past few years, South America underwent a deregionalisation process with regard to security, which led countries to promote intermestic security practices as an emerging strategy for the formulation of agendas and the sharing of policies between neighbouring countries in the region. With the World Health Organisation declaring SARS-CoV-2 a global pandemic, the region experienced a crisis of legitimacy among the current governments with major social mobilisations that led to the militarisation of internal security and consequent closure of borders using the argument of public safety. While South American countries sought answers in the face of low popular acceptance, old allies such as the United States reappeared on security agendas as the main partner in the fight against crime, thereby confirming their leadership in the hemisphere in matters of security and defence. This chapter has two objectives: on the one hand, to explain the deregionalisation of security prior to COVID-19, and on the other hand, to analyse the internal and intermestic security strategies generated during the pandemic in South America. In both cases, we argue that intermestic security and pragmatism are the results of the spread of cross-border transnational organised crime. At the same time, we explain that the militarisation of domestic security stems from the low level of political legitimacy of the current governments, which opened up their foreign policy to old but renewed alliances with the United States.