Lyme disease is the most significant vector-borne disease in the United States. Its southward advance over the last several decades has been quantified, and previous research has examined the potential role of climate change on the disease's expansion, but no research has considered the role of future land cover patterns upon its distribution. This research examines Lyme disease risk in the southeastern United States based on estimated land cover projections under four different Intergovernmental Panel on Climate Change Special Report Emissions Scenarios (IPCC-SRES) A1B, A2, B1, and B2. Results are aggregated to census tracts which are the basic unit of analysis for this study. This study applied previously established relationships between Lyme disease and land cover in Virginia to the projected land cover layers under each scenario. The study area, the southeastern United States, was defined from Level III Ecoregions that are present in Virginia and extend throughout the Southeast. Projected land cover data for each scenario were obtained from the USGS. The projected land cover datasets are compatible with the National Land Cover Dataset (NLCD) categories and had seventeen land cover categories. The raster datasets were reclassified to four broad land cover types: Water, Developed, Forest, and Herbaceous areas and the relationship between certain landscape configurations were analyzed using FRAGSTATS 4.2. Significant variables established in previous research were used to develop a spatial Poisson regression model to project Lyme disease incidence for each decade to the year 2100. Results indicated that potential land cover suitability for Lyme disease transmission will increase under two scenarios (A1B and A2) while potential land cover suitability for Lyme disease transmission was predicted to decrease under the other two scenarios (B1 and B2). Total area under the highest category of potential land cover suitability Lyme disease transmission was calculated for each year under each scenario. The A2 scenario experiences the most rapid acceleration of potential land cover suitability for Lyme disease transmission, with an average increase of 16,163.95 km² per decade, while the A1B scenario was projected to show an average increase of 3,458.47 km² per decade. Conversely, the B1 scenario showed an average decrease of 595.7 km² per decade and the B2 scenario showed the largest decrease of potential land cover suitability for Lyme disease transmission with an average decrease of 2,006.83 km² per decade. This study examined the potential spatial distribution of potential land cover suitability for Lyme disease transmission in the southeastern United States under four different future land cover scenarios. The results indicate geographic regions of the study area that are at greatest risk of potential land cover suitability for Lyme disease transmission under four different predictive scenarios developed by the IPCC. The A1B and A2 land cover projections are predicted to have an overall increase in areas where the Lyme disease transmission cycle will be enhanced by 2100 and the scenarios have a primary focus on economic development. Economic concerns outweigh environmental concerns for the A1B scenario, in addition to a high standard of living. The A2 scenario describes rapid population growth which results in high rates of land cover conversion to developed land; in addition, this scenario describes a reduction of environmental protection. The B1 and B2 land cover projections are predicted to have an overall decrease in areas of high Lyme disease transmission by 2100 and these scenarios have a central focus on environmental sustainability. The B1 scenario is characterized by a high environmental awareness which results in lower demand for forest products. A common theme for the B1 scenario is restoration and forest protection. Finally, the B2 scenario is described as improving local and regional environmental value which results in a high demand for biofuels and repossession of degraded lands, and an overall increase of forest cover. This study was the first to predict potential land cover suitability for Lyme disease risk and geographic distribution using projected land cover in the southeastern United States, and the results of this research can aid in the reduction of Lyme disease as it continues to expand in the south. / Master of Science / Lyme disease is the most significant vector-borne disease in the United States, recognized for its southward advance over the past several decades. Previous research has examined the potential role of climate change on the disease’s continued expansion at the northern extent of its distribution, but no studies have considered the role of future land cover scenarios upon its southward advance, despite a strong association between land cover and Lyme disease emergence. This research examines potential land cover suitability for Lyme disease transmission under projected land cover scenarios provided by the United States Geological Survey under four Intergovernmental Panel on Climate Change Special Report Emissions Scenarios: A1B, A2, B1, and B2. Based on previous research completed in Virginia, developed and herbaceous land cover, and the edges between both herbaceous and forested land in addition to the edges between herbaceous and developed land are all statistically associated with human Lyme disease occurrence. We use a similar statistical model developed in the previous research to quantify potential land cover suitability in the same level III ecoregions present in Virginia projected to their full extent to the south under different land cover scenarios in decadal increments from 2020 to 2100. Results demonstrated variation in potential suitable land cover for Lyme disease transmission depending on the specific scenario. Broadly, if future land cover patterns follow the A1B or A2 scenarios, an increase of suitable areas are to be expected for the Lyme disease transmission cycle. Conversely, if future land cover patterns follow the B1 or B2 scenarios, a decrease of suitable areas are to be expected for enhanced Lyme disease transmission. The results of this research can provide information to public health officials in these areas as the disease continues to expand to the south in the following decades.