BackgroundThe prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations.ObjectiveDetermine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2O2/I−) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo.AnimalsSixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd.MethodsIn vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2O2/I− system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo‐controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I− concentration.ResultsBovine herpesvirus‐1, parainfluenza‐3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2O2/I− reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax = 181 (1,420 μM I), T12, a sufficient concentration to inactivate these pathogens in vitro.Conclusions and Clinical ImportanceIn vitro, the LPO/H2O2/I− system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections.