Interpreting the health of ancient populations can be an arduous undertaking. Often, the only evidence available for such interpretation is the skeletal remains of past individuals. Paleopathologists examine these in order to garner a perspective of how previous groups responded to disease and also how humans and pathogens have coevolved and adapted to one another. The purpose of this study is to determine the presence of tuberculosis (TB) and treponematosis in the Orendorf population, a Middle Mississippian group who inhabited the central Illinois River valley from A.D. 1150-1250. The belief is that Orendorf will exhibit evidence of these pathologies in their skeletal remains, based upon the presence of TB and treponematosis in other Mississippian societies with comparable cultural manifestations (maize agriculture, trade, similar settlement patterns). Also determined in this investigation is the frequency of these diseases by calculating prevalence. The total number of individuals excavated in the Orendorf cemetery is 284. However, only adults are chosen for study, for a subsample of 117 individuals. The remains are subjected to macroscopic and radiological examination for skeletal markers of TB and treponematosis. Those who demonstrate suspicious-looking lesions are placed into one of two categories based upon the characteristics of the lesions.Possible lesions are suggestive of the diseases in question, but are ambiguous enough to prevent classification in the likely category, which likely fulfill the diagnostic criteria. Differential diagnosis, a rigorous methodology commonly employed in paleopathological research, is then applied to these cases in order to determine the responsible disease process. It is discovered that there are 2 possible and 1 likely cases of TB and 4 possible and 3 likely cases of treponematosis. Prevalence rates are 2.6% for TB and 6.0% for treponematosis, respectively. These results suggest that these disease were present in chronic form in Orendorf. When comparing the results to other Mississippian and non-Mississippian sites, it is found that there are no significant differences in the numbers of individuals affected, except when comparing TB in Orendorf to Norris Farms #36, a later Oneota population. In addition, future epidemiological investigations may be conducted on this population, in order to garner a more comprehensive view of their health.