The aim of this study was to evaluate the effects of two dietary supplements (monensin and a live yeast culture) on acid-base balance in steers maintained in a commercial feedlot system, considering effects over the finishing productive cycle. Steers (no. =42) were allotted randomly to one of the three study groups: (1) control group (no supplementation, C), (2) monensin supplementation (MON), and (3) live Saccharomyces cerevisiae strain 47 supplementation (SACC). Venous blood samples were collected for the measurement of acid-base parameters and l-lactate. Production parameters were also used as a complementary tool for understanding the internal changes associated with supplementation. During the finishing period, MON steers tended to gain more efficiently than C and SACC steers. In the C group, the finishing-period diet caused a progressive decline in blood bases, in line with the high-grain diet consumption. In contrast, supplemented animals did not show this trend, although lower HCO3− and base excess values were registered in SACC steers than in MON, indicating that ionophore supplementation is less effective for reducing blood base consumption than yeast supplementation. In our study, the lack of the expected response to yeast supplementation may be attributable to the high crude protein content of the ration, a common feature of commercial feedlot industries.