What was the biggest killer of the Sioux on reservation?

The biggest killer of the Sioux on reservations was disease, particularly tuberculosis and smallpox, exacerbated by poor living conditions, malnutrition, and a lack of medical care. The drastic changes to their lifestyle and diet, along with the stress of confinement, weakened their immune systems. These factors, combined with the effects of poverty and social disruption, led to significant mortality rates among the Sioux population on reservations.