The objectives were to ascertain whether a yeast cell-wall derivative that was 1.8% beta-glucan in combination with ascorbyl-2-polyphosphate could improve innate immunity and mediate transportation stress in neonatal calves, and to compare the 1.8% beta-glucan yeast cell-wall derivative with a more purified yeast cell-wall derivative (70% beta-glucan). Treatments were 1) an unsupplemented control (CNT); 2) 113 g of a 1.8% (approximately 2%) beta-glucan derivative of yeast cell walls plus 250 mg of l-ascorbic acid phosphate (BG2); or 3) 150 mg of a purified beta-glucan fraction from yeast cell walls (approximately 70% beta-glucan) plus 250 mg/feeding of l-ascorbic acid phosphate (BG70). Calves (n = 39) were transported for 4 h, placed in outdoor hutches, and randomly assigned to treatments. Treatments (mixed with a milk replacer) were individually fed twice daily for 28 d. Calves were offered calf starter, free choice, throughout the study. Weekly starter intake and BW were measured, and fecal samples were collected for Salmonella Typhimurium and Escherichia coli O157:H7 PCR analysis. Blood was collected immediately before transport (d 0) and on d 3, 7, 10, 14, 21, and 28 after transport. Starter intake and DMI were less (P < 0.05) at d 28 for the BG2 and BG70 treatments compared with the CNT treatment. Hematocrit percentages increased (P = 0.002) throughout the experiment. White blood cell counts (treatment x time interaction, P = 0.066) were less for the calves supplemented with BG70 than for those supplemented with BG2 (P = 0.01) or for CNT calves (P = 0.04) on d 28. Granulocyte counts changed (P = 0.04) throughout the experiment. A trend (P = 0.077) for a treatment x time interaction was detected for peripheral blood mononuclear cell counts (PBMC). Counts of PBMC were greater (P = 0.006) for the BG2 treatment compared with the CNT treatment on d 3. Calves given the BG70 supplement had fewer PBMC than those given the BG2 supplement on d 21 (P = 0.03) and 28 (P = 0.05). Fibrinogen concentrations were affected only by time (P = 0.002). Time effects were detected for phagocytosis (P = 0.005), oxidative burst (P < 0.001), expression of cluster of differentiation 18 (P = 0.001), and increased cluster of differentiation 18 (P = 0.006). Phagocytosis was less (P = 0.05) for calves in the BG70 group than for those in the CNT group. Percentage of calves positive for E. coli O157:H7 was greatest (P <or= 0.05) for those in the BG2 group on d 7 compared with those in the other treatments. The BG2 and BG70 supplements both increased feed intake, but only the BG2 supplement increased E. coli shedding on d 7, and the BG2 and BG70 supplements varied in modulating immune functions, indicating differences in yeast extract function.