Necrohemorrhagic enteritis (NHE), caused by Clostridium perfringens, predominantly affects white veal calves and usually has a fatal outcome. The C. perfringens α toxin is essential for lesion development, and as such, antibodies against this toxin are potentially protective. In the present prospective cohort study, we aimed to describe the seroepidemiology of C. perfringens α toxin under commercial veal calf rearing conditions to characterize the dynamics of the humoral immune response. Furthermore, we investigated the association between α toxin antibody development and carcass weight under the farming conditions for white veal calf production. From 2 to 24 wk of age, 40 male Holstein-Friesian calves were housed and reared under commercial veal calf conditions, receiving milk replacer and solid feed. Serum and fecal samples were collected at 4, 10, 12, 14, 18, 20, and 24 wk of age, and animals were weighed every 2 wk, up until 10 wk. At the end of the production period, animals were slaughtered and hot carcass weight (HCW) was determined. Antibody levels against C. perfringens α toxin were monitored over time. Upon arrival, 97.4% of the calves was seropositive. Antibody levels gradually declined, and a gap was observed between 14 and 20 wk of age, with an estimated nadir at 17.3 wk. Average daily gain was numerically higher for seropositive animals (0.95 ± 0.11 kg/d) than seronegative animals 0.85 ± 0.16 kg/d), resulting in a clear difference in HCW between calves that were seronegative and seropositive at the end of the study, as the latter weighed 13.4 kg more. Our data identified the critical window of maximum susceptibility to α toxin, potentially explaining why NHE-associated sudden death frequently manifests in calves aged 16 to 20 wk. The positive association between α toxin seropositivity and HCW suggests increased exposure to α toxin with solid feed intake. Taken together, the present study provides information relevant for the design of preventive strategies against NHE in terms of vaccination or nutritional management.