This paper presents an analysis of human remains from Tatham Mound, a dual-component mortuary site from central Gulf Coast Florida. The human remains from Tatham are significant because they come from a limited time period during the initial contact with Europeans at AD 1525–1550. Dietary reconstruction demonstrates that at the time of European contact, maize was not a predominant dietary item. Low frequencies for several dental and skeletal pathological indicators are consistent with relatively good health as compared to other Southeastern late prehistoric and protohistoric populations. Despite the limited time period represented by the mound population, critical interactions occurred between Native Americans and Spaniards, as indicated by skeletal elements severed by metal weapons. The Tatham population is significant because it is one of the earliest studied populations contacted by Europeans in North America, and the only one with well-documented sharp-force trauma that represents intergroup hostility. Am J Phys Anthropol, 2006. © 2005 Wiley-Liss, Inc.