It is estimated that up to 80% of the Aztec population, or around 15-20 million people, died from smallpox following the Spanish conquest of the Aztec Empire in the early 16th century. Smallpox was introduced to the Americas by European explorers and colonists and quickly spread among the indigenous populations, who had no natural immunity to the disease. The devastating loss of life caused by smallpox severely weakened the Aztec Empire and played a significant role in its eventual defeat by the Spanish.