The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers (n = 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BWDEX was intravenously administered at 1000 h on d −3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d −4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at −74, −50, and −26 h; at 0.5-h intervals from −4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction (P < 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d −3 and 0, respectively. A treatment × time interaction (P < 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers (P < 0.001) yet decreased lymphocytes in CHR steers (P = 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased (P < 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosin-ophils were greater (P < 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction (P = 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced (P ≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed (P ≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed (P ≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.