Plague is an infectious disease caused by the bacterium Yersinia pestis. It has been responsible for widespread pandemics in the world throughout history. In this regard, the plague began to affect the Ottoman Empire in phases from the middle of the 15th century and reached its peak in almost the entire empire at the end of the 16th century. Since it is not possible to deal with this whole process in one article, this article focuses on the end of the 16th century, when the plague intensified in almost the whole empire. However, this article aims to mainly analyse the process, conditions, dynamics and effects of this epidemic based on the Spanish Empire with the comparative historical method. The plague appeared in the Ottoman Empire from t...