Objective: To evaluate associations between economic and performance outcomes with the number of treatments after an initial diagnosis of bovine respiratory disease (BRD) in commercial feedlot cattle. Animals: 212,867 cattle arriving in a Midwestern feedlot between 2001 and 2006. Procedures: An economic model was created to estimate net returns. Generalized linear mixed models were used to determine associations between the frequency of BRD treatments and other demographic variables with economic and performance outcomes. Results: Net returns decreased with increasing number of treatments for BRD. However, the magnitude depended on the season during which cattle arrived at the feedlot, with significantly higher returns for cattle arriving during fall and summer than for cattle arriving during winter and spring. For fall arrivals, there were higher mean net returns for cattle that were never treated ($39.41) than for cattle treated once ($29.49), twice ($16.56), or ≥ 3 times (−$33.00). For summer arrivals, there were higher least squares mean net returns for cattle that were never treated ($31.83) than for cattle treated once ($20.22), twice ($6.37), or ≥ 3 times ($−42.56). Carcass traits pertaining to weight and quality grade were deemed responsible for differences in net returns among cattle receiving different numbers of treatments after an initial diagnosis of BRD. Conclusions and Clinical Relevance: Differences in economic net returns and performance outcomes for feedlot cattle were determined on the basis of number of treatments after an initial diagnosis of BRD; the analysis accounted for the season of arrival, sex, and weight class.