Vaccination of newly received cattle against respiratory pathogens is a common practice in the stocker or feedlot setting; however, this practice may induce an acute inflammatory or febrile response that could affect clinical presentation or transiently reduce performance. Our objective was to determine if different combination viral-bacterial respiratory vaccines affect the leukotoxin (LKT) antibody concentration, acute phase response, rectal temperature (RT), or gain performance. A total of 30 clinically healthy beef heifer calves (BW = 222.3 ± 27.1 kg) were stratified by pre-trial serum antibody against Mannheimia haemolytica (MH) whole cell wall, then assigned randomly to 1 of 3 vaccine treatment regimens consisting of (1) Pyramid 5 + Presponse SQ (P5PS; n = 10), (2) Bovi-shield Gold One Shot (BGOS; n = 10), or (3) unvaccinated control (CON; n = 10). Heifers were housed in a single pen, and blood, BW and RT were collected on d 0, 4, 7, 14, 28, 42 and 56. A treatment x d interaction was observed for MH-specific LKT (P < 0.001). Cattle administered either of the vaccines had greater LKT antibody concentrations than CON on d 14 and 28 (P ≤ 0.04), whereas BGOS was greater than CON on d 7 (P = 0.03) but did not differ from P5PS (P = 0.49). No differences were detected for RT (P = 0.85) or ADG (P ≥ 0.33), which averaged 1.17, 1.11 and 1.23 kg/d for P5PS, BGOS, and CON, respectively from d 0 to 56. Respiratory vaccination affected serum haptoglobin (Hp) concentration; P5PS exhibited greater Hp concentrations than CON (P = 0.01) but was not different from BGOS (P = 0.53). No difference in serum ceruloplasmin was observed (P = 0.88). Results indicate that either vaccine produced a greater LKT antibody and Hp response compared with CON, but RT and performance were not affected. Respiratory vaccines may have slight inflammatory effects when administered to clinically healthy cattle, yet further research is warranted to elucidate vaccine-induced inflammation in highly stressed cattle.