The Naples Plague is a plague epidemic that occurred in Italy from 1656 to 1658, which caused a devastating blow to the population of Naples.[1][2] The epidemic mainly affects the central and southern regions of Italy. Some researchers estimate that 1.25 million people died from the plague in the Kingdom of Naples in Italy, which is one of the deadliest epidemics in history.[1][3][4] In Naples alone, approximately 150,000 to 200,000 people died of disease in 1656, accounting for at least 50% of the city’s total population.[3][4][5][6] The plague epidemic has severely affected the economic and social structure of Naples and other disaster-stricken areas.[2][4][7]