<p>This study investigated the effects of colostrum dry matter (DM), fat, solids-non-fat (SNF), protein, and lactose contents as well as colostrum and serum immunoglobulins of calves (IgG, IgA, IgM), IGF-1, and lactoferrin concentrations on the morbidity, mortality and growth performance of Anatolian buffalo (<i>Bubalus bubalis</i>) calves until 180 days old (weaning). A total of 85 female and male calves were utilised in the present study. The main components and bioactive substances in colostrum were analysed using a milk analyser and ELISA, respectively. Calf serum samples were collected at 24–48&#xa0;h and 28 d postpartum, and subsequently analysed via ELISA. Two groups, High and Low, were created as those above and below the mean of the parameters examined. Calves with high circulating concentrations of IgG at 24–48&#xa0;h and IGF-1 and lactoferrin at 28 d during the neonatal period (0–30 d and 31–60 d) had a lower prevalence of diarrhoea than those with low concentrations. Calves with high circulating concentrations of all Igs (at 24–48&#xa0;h) had lower mortality between 0 and 180 d. Calves fed with colostrum with high DM, SNF, protein, IgG, IGF-1 and lactoferrin content were associated with high growth rate during different phases up to weaning, regardless of the volume of colostrum delivered. Consequently, variations in the concentration of some bioactive substances in colostrum and circulation can result in low disease and mortality, as well as high growth rate.</p>