Abstract Latin America has always been a region of great interest not only for its rich-multicultural heritage, and diverse flora and fauna, but also for its natural resources that have become valuable commodities worldwide. In this paper an exergy-based analysis is used to investigate the cost of mineral depletion. By applying exergy replacement costs (ERC), a concept based on the Second Law of Thermodynamics, ERC determines the cost in exergy terms to recover minerals to its prior conditions with the current best available techniques when they have been completely dispersed after their usage. Such an assessment is a robust tool when evaluating natural resources in a country or region. We show that by using the above-mentioned methodology, it is possible to objectively quantify the loss of mineral wealth in Latin America associated to mineral extraction. Our study shows that the loss of mineral wealth in 2013 in the region was not compensated in comparison to the revenues obtained for the sale of minerals. Therefore, to establish a sustainable future scenario for the production of minerals in Latin America, a new framework for trading and management of fuel and non-fuel minerals is necessary.