The objective of this study was to evaluate growth and performance of postweaning heifers supplemented with monensin (MON), sodium butyrate (SB), or the combination of MON and SB (MSB) compared with heifers not receiving these feed additives. Forty Holstein heifers [mean age 84.2 ± 1.2 d; body weight (BW) 99.8 ± 10.8 kg (mean ± SD)] were housed in a freestall barn, blocked by birth date, and randomly assigned to 1 of 4 treatments in a randomized complete block design. Treatments were (1) 100 g of soybean meal carrier (control; CON); (2) 0.75 g of SB/kg of BW + carrier (SB); (3) 1 mg of MON/kg of BW + carrier (MON); (4) 1 mg of MON/kg of BW + 0.75 g of SB/kg of BW (MSB). Data were analyzed using single degree of freedom contrasts evaluating CON versus additives (ADD), SB versus MON, and SB and MON versus MSB. Treatments were hand-mixed daily. Feed and orts were measured daily and frozen at -20°C. Orts samples were subsampled for dry matter (DM) determination, and total mixed ration samples were taken weekly and composited monthly for DM and nutrient analysis. Initial BW, heart and paunch girths, body length, blood samples, and fecal coccidia counts were measured before the start and weekly during the 12-wk trial. Blood samples were analyzed for glucose, plasma urea nitrogen (PUN), and ketone concentrations. Apparent total-tract nutrient digestibility was determined from d 21 to 27 and from d 63 to 69 using acid detergent insoluble ash as a marker. Daily dry matter intake (DMI) and metabolizable energy intake were increased in ADD compared with CON, and average BW, final BW, and heart girth tended to increase. Whereas MSB tended to be greater than SB and MON for heart girth, feed efficiency was greater with MON compared with SB. Compared with CON, ADD decreased coccidia counts. No effect of treatment on PUN was detected. Monensin and SB tended to have greater plasma glucose than MSB did. Average blood ketone concentrations were greater with ADD versus CON, in SB versus MON, and in MSB versus SB and MON. During the wk-3 digestibility phase, DMI tended to be greater in heifers fed SB versus MON, as well as in heifers fed MSB versus SB and MON. Digestibility of nutrients were similar, except that starch digestibility was increased in heifers fed MSB versus SB and MON. During the wk-9 digestibility phase, DMI and digestibility of nutrients were similar, except NDF, which tended to be greater in CON than in ADD. Overall, ADD resulted in positive growth and reduced coccidia compared with CON.