Infectious respiratory diseases of ruminants are a serious health and economic problem for U.S. agriculture. In cattle alone, bovine respiratory disease complex (BRDC) costs the feedlot industry approximately 1 billion USD annually. Respiratory disease results in inflammation and is associated with an increase in acute phase proteins in peripheral blood. Haptoglobin (HPT) is an acute phase protein synthesized in the liver in response to stressful situations, injury, and disease. Our objectives were to determine if HPT concentrations in plasma differed between sham- and mass-medicated treatment groups and if it differed between animals presenting with BRDC and those that remained healthy throughout a 28-day trial regardless of antibiotic use. Sixty head of cattle were purchased at each of three Southeastern sale barns for a total of 180 animals on trial. Cattle were transported up to 1,354 km to a feeding facility in the Central U.S. where they were randomly allocated within source to one of two treatments, mass-medication with gamithromycin (n = 90) or sham saline-injection treatment (n = 90). Blood samples were collected for plasma at day 0 (at sale barn), day 1 (at Central U.S. facility), day 9, and day 28. Cattle presenting with BRDC were also sampled for plasma at the time of diagnosis and 5 days later. The plasma samples were assayed for bovine HPT using a commercially available ELISA. Of the 180 cattle on trial, 28 presented with BRDC. These cases were matched with control (healthy) animals from the same treatment, pen, and sale barn. Preliminary data demonstrate an increase in HPT concentrations after transportation (day 1) as compared to days 0, 9, and 28. There was also a significant difference in HPT concentrations between cattle diagnosed with BRD and case controls. In addition, gamithromycin decreased HPT concentration on day of BRDC diagnosis (P = 0.06).