To determine whether supplementation of anti-phospholipase A antibody (aPLA) would alter voluntary DMI, feed efficiency (FE), acute-phase protein concentration, and blood differentials (BD) due to a change in diet from a forage-based to a grain-based diet, individual daily DMI was measured on 80 cross-bred steers during a 141-d period. On d 0, steers were blocked by BW and randomly assigned to receive a growing forage diet containing 1) no additive (CON; = 20), 2) inclusion of 30 mg of monensin and 8.8 mg of tylosin per kg of diet DM (MT; = 20), 3) inclusion of an aPLA supplement at 0.4% of the diet DM (0.4% aPLA; = 20), and 4) inclusion of an aPLA supplement at 0.2% of the diet DM (0.2% aPLA; = 20). On d 60, steers were transitioned into a grain-based diet (90% concentrate) over a 21-d "step-up" period while continuing to receive their supplement treatments and were maintained on the high-grain diet until the end of the trial on d 141. On d 0, 60, 81, and 141, individual shrunk BW was recorded. Blood samples were collected on d 60, 63, 65, 67, 70, 72, 74, 77, 79, 81, and 84 for determination of concentration of plasma ceruloplasmin, haptoglobin, and BD. During the growing forage-diet period, steers from the 0.2% aPLA and 0.4% aPLA treatments had lower ( < 0.05) residual feed intake (RFI; -0.12 ± 0.13 and -0.22 ± 0.13 kg/d, respectively) than steers from the CON treatment (0.31 ± 0.13 kg/d). During the grain-based diet period, the 0.2% aPLA (-0.12 ± 0.10 kg/d), 0.4% aPLA (0.36 ± 0.10 kg/d), and MT (0.10 ± 0.10 kg/d) steers had greater ( = 0.04) RFI than CON steers (-0.37 ± 0.10 kg/d). During the transition phase, white blood cell counts were greater ( = 0.04) for the 0.2% aPLA treatment (13.61 × 10 ± 0.42 × 10 cells/μL) than the 0.4% aPLA and MT treatments (12.16 × 10 ± 0.42 × 10 and 12.37 × 10 ± 0.42 × 10 cells/μL, respectively) and concentrations of lymphocytes also were greater ( = 0.01) for the 0.2% aPLA treatment (7.66 × 10 ± 0.28 × 10 cells/μL) than the 0.4% aPLA and MT treatments (6.71 × 10 ± 0.28 × 10 and 6.70 × 10 ± 0.28 × 10 cells/μL, respectively). Concentrations of plasma ceruloplasmin and haptoglobin were reduced ( < 0.05) for CON compared to aPLA steers (22.2 ± 0.83 vs. 24.4 ± 0.83 mg/dL and 0.18 ± 0.05 vs. 0.26 ± 0.05 mg/mL, respectively). Supplementation of aPLA improved FE of steers fed a forage-based growing diet but not when feeding grain-based diets. The 0.4% aPLA and MT treatments had decreased white blood cell counts and concentration of lymphocytes during the transition period compared to the 0.2% aPLA treatment, and CON steers had reduced concentrations of plasma ceruloplasmin and haptoglobin during the diet transition phase.