One hundred and eighty crossbred beef steers (406.0 ± 2.2 kg) were used to determine the impact of a novel direct-fed microbial (DFM) on growth performance, carcass characteristics, rumen fermentation characteristics, and immune response in finishing beef cattle. Steers were blocked by body weight and randomly assigned, within block, to 1 of 2 treatments (3 replicates/treatment: 30 steers/replicate). Treatments included: 1) no DFM (control) and 2) DFM supplementation at 50 mg∙animal-1∙d-1 (BOVAMINE DEFEND® Plus). All steers were fed a high-concentrate finishing diet and individual feed intake was recorded daily via the GrowSafe® system. Body weights were collected every 28 d. On d 55, 10 steers per pen were injected with ovalbumin (OVA). Jugular blood samples were collected from each steer on d 0, 7, 14, and 21 post-injection. On d 112, the same steers were injected again with OVA and intramuscularly with a pig red blood cell solution. Jugular blood samples were collected from each steer on d 0, 7, 14, and 21 post-injection. On d 124 rumen fluid was collected from 3 steers per treatment and used to estimate in vitro rumen fermentation characteristics. Equal numbers of steers per treatment were transported to a commercial abattoir on d 145, 167, and 185 of the experiment, harvested, and carcass data collected. Initial body weight (BW) was similar across treatments. On d 28 and 55, steers receiving DFM had heavier BW (P < 0.01) compared to controls. Average daily gain was greater in DFM-supplemented steers from d 0 to 28 (P < 0.01) and d 0 to 55 (P < 0.01) of the experiment compared to controls. Overall dry matter intake was greater (P < 0.04) and overall feed efficiency was similar in DFM-supplemented steers compared to controls. Dressing percentage (P < 0.02) was greater in steers receiving DFM compared to controls. Antibody titers to injected antigens were similar across treatments. However, red blood cell superoxide dismutase activity was greater (P < 0.05) in DFM-supplemented steers compared to controls. In vitro molar proportions of isobutyric and butyric acid were greater (P < 0.01) and dry matter (DM) digestibility tended (P < 0.07) to be greater in rumen fluid obtained from steers supplemented with DFM. These data suggest that BOVAMINE DEFEND® Plus supplementation improves growth performance during the initial period of the finishing phase, increases overall dry matter intake and dressing percentage, and may impact antioxidant status in beef cattle.