Populations of plants can vary dramatically in the number of individuals they contain. Small populations are often at greater risk of extinction, making it important to understand why some populations consist of hundreds of plants while others contain less than twenty. Factors that affect germination, seedling establishment, growth or fecundity will likely have a significant effect on population size. For plants, such factors likely include interactions with soil microbes, such as fungi, and aspects of soil chemistry and composition. The great blue Lobelia, an herbaceous perennial plant found in the Eastern United States, exhibits a high degree of variation in population size, with most populations containing fewer than 100 plants. We sampled soils from seven large (> 100 individuals) and seven small (< 100 individuals) populations, and have characterized patterns of soil moisture, texture, chemical composition, and microbial diversity among these populations. Soil types were very diverse ranging from 0-90% sand with small populations having much lower among-site variability than large populations. Clay content ranged from 0.6-42% with small populations exhibiting lower within-site variability, implying greater spatial heterogeneity in large populations. Measurements of moisture content and labile organic matter also suggest the possibility of larger among-site variability in small populations than in large populations. In general we found that chemical and biological properties do differ significantly between populations of different sizes, which may indicate an important role of soil properties in the regulation of population size of L. siphilitica.