After weaning, the transition from individual housing to group housing (commingling) is stressful for calves and increases the risk of respiratory disease during this period. Prebiotics can include mannan-oligosaccharide (MOS) and β-glucan (BG) which may help improve calf health and performance. Therefore, the objectives of this study were to determine if a daily bolus dose of oral prebiotics (20% MOS; 10% BG) influence feed intake, body weight gain, or adaptive immunity in Holstein heifer calves (n = 60) during the transition from individual hutches to pens of 3. One week before commingling, calves (age 52 ± 4.0 SD d; body weight 83 ± 14.92 SD kg) were randomly assigned to daily treatments of either 4 g of prebiotic (Preb) dissolved in 15 mL of molasses or control (Con; 15 mL of molasses only) for 7 weeks. Calves were fed ad libitum TMR top-dressed with 9 pounds of 18% CP calf starter once per day with refusals collected and measured daily. Calves were weighed and measured weekly. All calves were administered an innocuous protein injection, ovalbumin (OVA; subQ; 0.5 mg/mL), at commingling and 4 weeks after commingling. Blood was collected 2 weeks after OVA to measure primary and secondary OVA-specific IgG and IgA responses. Prebiotic-fed calves ate more than control-fed calves 2 weeks after commingling (3.18 vs. 3.06 ± 0.034 kg/d; P = 0.015). Prebiotic calves also gained more weight 3 weeks (ADG 0.90 vs. 0.86 ± 0.060 kg/d; P = 0.037) and 6 weeks post-commingling (ADG 1.08 vs. 0.96 ± 0.060 kg/d; P = 0.025). In addition, the interaction between treatment and week affected F:G (P = 0.044) with preb-calves having lower F:G 1, 3, and 6 weeks post-commingling. The Preb-calves had a greater primary IgA response to OVA than Con-calves (P = 0.0315), but no differences were observed for IgG (P = 0.8289). Prebiotic supplementation may improve calf performance and adaptive immunity in the transition to group-housing situations post weaning.