For centuries, smallpox was one of the most dreaded diseases among the population. However, during the eighteenth century, a greater scientific interest was observed among physicians in analyzing and reflecting on this and other diseases, their underlying causes, treatments, medicines and the way to prevent them. In response, the Crown introduced public policies aimed at managing the risk of contagion. Meanwhile, within the Hispanic Monarchy, a process of change was underway that sought to redefine power relations within the context of corporate powers. This resulted in a shift towards a more direct and centralized form of governance of the monarch through acts of government, with the aim of promoting the collective happiness of the subjects, which in the field of public health derived into how the Crown reacted to critical situations, such as smallpox epidemics, within the context of ongoing scientific advancement.