The objective of this research was to determine the effect of an acute vs. chronic stress model on serum antibody titer and acute phase responses. Seronegative beef steers (n = 32; 209 ± 8 kg) were stratified by BW and assigned randomly to 1 of 3 treatments (1) Chronic stress (CHR), 0.5 mg/kg BW dexamethasone (DEX) administered i.v. at 1000h on d −3 to 0; (2) Acute stress (ACU), 0.5 mg/kg BW DEX administered i.v. at 1000h on d 0 only; or (3) Control (CON), no DEX. On d −4, steers were fitted with jugular catheters and placed into individual stanchions in an environmentally controlled facility. At 1200h on d 0, steers were administered a modified-live virus respiratory vaccine containing isolates of infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV) and parainfluenza-3 virus (PI3V). On d 4, cattle were transported (177 km) to an isolated facility and housed in a single pen. Serum was harvested from d 0, 7, 14, 21, 28, 35, 42, and 56 and subsequently used to determine IBRV-, BVDV-, BRSV-, and PI3V-specific antibody titers. Additionally, serum from d −2, 0, 1, 3, 7, and 14 was used to quantify haptoglobin (Hp) and ceruloplasmin (Cp) concentrations. There was a trt × d interaction (P < 0.01) such that CHR steers had a greater (P ≤ 0.07) BVDV antibody titer from d 14 to 28; whereas, CHR was greater (P = 0.06) than ACU on d 56. Moreover, IBRV antibody titers were increased beginning on d 14 for CHR and d 28 for ACU, and remained elevated through d 56 compared with CON (P ≤ 0.03). Stress treatment altered Hp such that CON exhibited a greater (P < 0.01) Hp concentration than CHR but was not different from ACU (P = 0.16). On d 3, Cp was greatest for CON, intermediate for ACU, and least for CHR (trt × d; P ≤ 0.01). Results suggest that immunosuppressive conditions in CHR and ACU may have allowed enhanced viral replication from the vaccine, resulting in a greater antibody titer response. Data further indicate that DEX administration blunted the acute phase response and these alterations were particularly evident in the CHR stress model.