Following the recent invasion of bovine tuberculosis (BTB) into the Kruger National Park, South Africa, we conducted a study on the maintenance host, African buffalo, to investigate associations between BTB prevalence and calf:cow ratio, age structure, body condition, and endoparasite load. Statistical analyses compared herds of zero, medium (1–40%), and high (>40%) BTB prevalence. To control for ecological variation across the park we collected data in northern, central, and southern regions and restricted some analyses to particular regions of the park. Body condition declined over the course of the 2001 dry season, and buffaloes in the southern region of the park, with the highest BTB prevalence, were in worse condition than buffaloes in the northern region (which receives less annual rainfall but is still virtually BTB-free). Herd-level analyses of the entire park, the south and central regions, and just the southern region all indicated that herds of higher BTB prevalence were in worse condition and lost condition faster through the dry season than herds of lower BTB prevalence. Fecal endoparasite egg counts increased during the dry season and were associated with both decreased body condition and increased BTB prevalence. Although we did not detect any obvious effect of BTB on the age structure of the buffalo population, our findings indicate early symptoms of wider scale BTB-related ecological disturbances: buffalo herds with high BTB prevalence appear more vulnerable to drought (because of a decrease in body condition and an increase in endoparasite load), and because lions selectively kill weak buffaloes their prey base is accumulating a disproportionately high prevalence of BTB, to which lions are susceptible.