What caused the death of so many settlers in Jamestown from 1607-1611? The death of so many settlers was caused by the unsuitable environment, the lack of certain settler skills and occupations, and the deteriorating Powhatan-English relationship. The death of so many settlers was caused by the unsuitable environment of the settlement. The location of Jamestown was chosen next to the James River so that the settlers could have a good source of water for food, drinking, transportation, and irrigation. However, this was not the case. Fresh water was scarce due to the high tides, which pushed the salt water from the Chesapeake Bay into the James River. This caused the water in the James River to become brackish. The brackish water spread disease and caused settlers to have salt water sickness. As a result of