Diseases are one of the main yield-limiting factors of soybean production that farmers must contend with every year. In Kentucky, estimated annual losses due to diseases over the last 5 years have averaged over 7.2 million bushels of soybeans, which has an approximate value of nearly $68 million. To protect against yield losses caused by diseases, soybean farmers actively manage these diseases by utilizing inputs such as fungicide and nematicide seed treatments and foliar fungicides. In some cases, utilizing these disease management inputs will result into a greater return on investment (ROI), while in other cases, these inputs may just be an added cost that does not result into increased yields or ROI. Field research trials were established at the University of Kentucky Research & Education Center (UKREC) near Princeton and at the Western Kentucky University Farm near Bowling Green in 2021 to evaluate the effect of different disease management practices on soybean yield and economic benefit. The experiment evaluated different seed-applied treatments and foliar-applied fungicides. Seed treatments included untreated seed, a fungicide + insecticide treatment (CruiserMaxx Vibrance), and the fungicide + insecticide treatment with a nematicide/sudden death syndrome treatment added (CruiserMaxx Vibrance + Saltro). Foliar-applied treatments included a non-treated check, a fungicide that contained “off-patent” active ingredients (azoxystrobin + propiconazole), and a “premium” fungicide (Miravis Top). Foliar fungicides were applied at the R3 growth stage (beginning pod stage). At each location, plant emergence, disease severity, and yield data were collected from each replicated treatment combination. An economic analysis was conducted using the yield responses relative to the non-treated check (no seed treatment, no foliar fungicide treatment), and the associated retail prices and application costs of the applied products and a soybean marketing price of $12.70 per bushel. The data were statistically analyzed using specialized software to evaluate for significant differences at a 95% confidence level. No statistically significant differences among treatments were observed, but some of the numerical differences were interesting. Overall, average yields were very high for all treatments (>90 bushels/acre) (Figure 1). Regardless of seed treatment utilized, the numerically highest yield achieved was with the “premium” foliar fungicide (Figure 1). Similarly, the numerically highest net economic benefits were achieved when the “premium” foliar fungicide was applied (Figure 1). It is important to note that the results reported here are from only one growing season at two locations. To be able to make broader conclusions, this research needs to be repeated across additional growing seasons and locations to better account for the effect of different environments and geographies. Understanding the disease risk for individual soybean fields by knowing the susceptibility of varieties being planted, accounting for rotating crops vs. continuous soybean, testing soil for soybean cyst nematode egg populations, and actively scouting for diseases during the season will help provide the best information that can be used to make soybean disease management decisions.