The objective of this study was to determine the effects of an immunomodulatory feed ingredient during post-weaning on growth and cortisol concentrations of beef heifers. Commercial Angus heifers (n = 72) from 2 AI sires were blocked (n = 9) by BW and randomly assigned to one of 2 pens per block. Each pen (4 heifers/pen) per block was randomly assigned to either one of 2 treatments, Celmanax (CEL) or corn germ (CON). The heifers were fed a commercial total mixed ration (TMR) twice daily from d 0 to 60 to gain 0.75 kg/d. The feed was top-dressed once daily with either 72g of Celmanax (CEL) or corn germ (CON) per pen. Body weight (BW) was collected on d -1, 0, 15, 30, 45, 60, and 61. Blood samples were collected on d 0, 15, 30, 45, and 60. Two heifers per pen (n = 32) were randomly selected for a transportation challenge to evaluate stress response on d 62 or 63 of the study. Sixteen heifers (n = 8 CEL; n = 8 CON) were randomly selected for a corticotropin-releasing hormone/arginine vasopressin (CRH/AVP) challenge and an intravenous glucose tolerance test (IVGTT) on d 64 and 67 of the study. The pen was the experimental unit, and data were analyzed by ANOVA or repeated measures analysis as appropriate. Feed efficiency and BW gain were increased (P = 0.04) in CEL heifers compared to CON heifers. Serum cortisol concentrations were decreased (P < 0.01) in CEL heifers compared to CON heifers on d 30 to 60 post-weaning. Serum cortisol concentrations were decreased (P < 0.05) in CEL heifers compared to CON heifers throughout the transportation challenge. Serum cortisol concentrations were decreased (P < 0.05) in CEL heifers compared to CON heifers during the CRH/AVP challenge from 60 to 150 min post-infusion. Treatment did not influence (P = 0.29) plasma insulin or glucose (P = 0.63) concentrations during the IVGTT. In summary, supplementation of Celmanax post-weaning increased BW gain and reduced cortisol concentrations in challenged beef heifers.