The present study was conducted to determine if a selenium deficiency affects the primary and secondary humoral immune response of calves challenged with infectious bovine rhinotracheitis virus (IBRV) and to evaluate changes in glutathione peroxidase (GSH-Px) and creatine phosphokinase activities associated with selenium deficiency and viral stress. Treatments included 1) +Se (0.2 mg/kg diet) and 2) -Se (0.03 mg/kg diet). Calves were adapted to their assigned diets during an 84-d depletion period. By d 42 of the depletion period, whole-blood GSH-Px was lower for -Se calves than for +Se calves. Differences between treatments in plasma GSH-Px were observed by d 14. On d 84, Se-dependent GSH-Px activity in liver was higher in +Se calves. After depletion of -Se calves, animals in both treatments were intranasally inoculated with IBRV on d 0 and 35 of the 70-d challenge phase. Whole-blood and plasma GSH-Px increased after IBRV inoculation in +Se calves but not in Se-deficient calves. Serum IgM was higher for +Se calves throughout the challenge phase. Serum IgM increased in both treatments after primary IBRV inoculation but was unaffected by secondary challenge. Serum IgG was not affected by selenium status but increased in both treatments after secondary IBRV challenge. Serum IBRV antibody titers increased after inoculation on d 0 and 35. By d 49, IBRV antibody titers were higher for +Se calves than in Se-deficient calves. These results indicate that selenium deficiency may depress the immune response of calves challenged with a foreign pathogen.