Abstract Difructose anhydride (DFA) III is an indigestible disaccharide that promotes paracellular absorption of calcium, magnesium, and other minerals in the intestine by acting on epithelial tight junctions. This study aimed to elucidate the effect of DFA III on serum IgG concentration. One hundred and twenty Holstein and Holstein/Japanese Black crossbred calves were randomly divided into 4 groups of 30 to receive untreated colostrum (DFA0) or colostrum containing 3, 6, or 18 g of DFA III (DFA3, DFA6, or DFA18, respectively). At 24h after birth, both serum IgG (ranging from 16.4 to 21.2mg/mL) and apparent efficiency of absorption (26.0 to 37.2%) showed increases with the amount of DFA III intake. By multiple regression analysis, the standardized partial regression coefficient for DFA III was 0.25, the second highest following that for the colostrum IgG concentration (0.80), indicating a positive effect of DFA III on serum IgG. A positive linear regression was found between colostrum IgG and serum IgG concentrations at 24h of age. These results indicate that IgG absorption occurred as a nonsaturable process, which might be characteristic of gradient-dependent paracellular transport. Thus, it was concluded that DFA III improves not only minerals but IgG absorption in calves.