It cannot be emphasized enough that Native American people were subjected to horrific treatment upon the arrival of European explorers and conquistadors in the 1500s. The Spanish instituted the encomienda system where conquistadors controlled large sections of the land and took on the roles of feudal lords. Natives were forced to work the land or in the mines.
While we have primary sources detailing massacres, instances of natives being worked to death, and other atrocities the number one killer of natives during the exploration and early colonization period was disease. It is the number one cause of the severe population decrease of natives during those years.