The objective of this study was to determine the effect of varying levels of sodium butyrate (SB) on growth, nutrient digestibility, and health of post-weaned heifers. Forty Holstein heifers (84 ± 2.8 d of age) with body weights (BW) of 100.9 ± 11.2 kg were enrolled in a 15 wk study and blocked by birth date in a randomized complete block design. Treatments were 100 g of soybean meal carrier served as a control (CON); 0.25 g SB/kg of BW + carrier (0.25SB); 0.50 g SB/kg of BW + carrier (0.50SB); 0.75 g SB/kg of BW + carrier (0.75SB). Treatments were hand-mixed into a total mixed ration daily. Initial BW, hip and withers heights, heart girth and body length were measured before treatment and every week thereafter. From blood samples collected, plasma urea nitrogen and BHB concentrations were determined before treatment and weekly thereafter. Fecal samples were taken before treatment and every other week for coccidia counts. Data collected before treatment were used as covariates in the final analysis using the MIXED procedure of SAS. Apparent total-tract nutrient digestibility was determined using chromium oxide. Heifers underwent this phase from 47 to 54 d on study. There was no effect of SB on nutrient digestibility, however, increasing SB levels had a tendency to improve digestibility of acid detergent fiber (P = 0.08). Daily DMI were not different between treatments. However, ADG were 1.16, 1.15, 1.17, and 1.24 kg/d (P = 0.12) for CON, 0.25SB, 0.50SB, and 0.75SB, respectively, which led to a trend in improved feed efficiency (P = 0.08). Sodium butyrate had a positive effect on average BW and overall BW gain (P = 0.04; P = 0.02, respectively). Sodium butyrate had no effects on skeletal growth and plasma urea nitrogen concentrations (P > 0.05). Concentrations of BHB increased with increasing SB levels (P < 0.05). Fecal samples indicated the presence of coccidia, but counts were inconsistent within treatments. Sodium butyrate supplementation offers positive results in growth performance and feed efficiency of post-weaned heifers.