We evaluated the effects of metabolizable protein (MP) supply on growth performance, and post-vaccination measurements of humoral immune response of beef steers. Angus steers (n = 36; 231 ± 21 kg; 184 ± 18 d) were weaned on d 0, stratified by weight and age on d 7, and randomly assigned into 1 of 18 drylot pens (2 steers/pen). Treatments were assigned to pens (6 pens/treatment), and consisted of isocaloric, corn silage-based diets formulated to provide 85, 100 or 115% of the daily MP requirements. Diets were offered at 2.1% of BW (DM basis) from d 7 to 49. Steers were vaccinated on d 21 and 35 with modified-live and killed vaccines (Select-Vac, Zoetis). Blood samples were collected from jugular vein on d 0, 21, 35 and 49 to determine the plasma cortisol concentrations, and serum titers against bovine viral diarrhea virus-1b (BVDV1b), infectious bovine rhinotracheitis (IBR) and Mannheimia haemolytica leukotoxin. Data were analyzed using GLIMMIX procedure of SAS, and pen(treatment) as random effect. Body weight differed only on d 49, and was greatest (P ≤ 0.05) for 115MP, least for 85MP and intermediate (P ≥ 0.21) for 100MP steers (297, 278 and 290 ± 7 kg, respectively). From d 7 to 49, 100MP and 115MP steers had similar ADG (P = 0.13), but both had greater (P < 0.001) ADG than 85MP steers (1.20, 1.35 and 0.83 ± 0.068 kg/d, respectively). Plasma cortisol concentrations were greater (P ≤ 0.03) for 85MP vs. 100MP and 115MP steers on d 21 and 35. Serum BVDV1b titers were greatest (P ≤ 0.02) for 115MP, and similar (P = 0.37) between 85 and 100MP steers (5.8, 3.7 and 3.0 ± 0.60 base 2 log, respectively). Mean serum M. haemolytica leukotoxin titers were greater (P = 0.05) for 85MP vs. 100MP and 115MP steers (3.12, 2.39 and 2.49 ± 0.21 ng/antibody bound, respectively). Hence, a 15% MP deficiency increased plasma cortisol, and both factors may have suppressed innate immune system leading to greater multiplication of endogenous M. haemolytica and a compensatory greater production of serum M. haemolytica leukotoxin titers. In contrast, 15% MP excess enhanced growth performance and increased serum BVDV1b titers of beef steers.