Co-infections are common in natural populations and interactions among co-infecting parasites can significantly alter the transmission and host fitness costs of infection. Because both exposure and susceptibility vary over time, predicting the consequences of parasite interactions on host fitness and disease dynamics may require detailed information on their effects across different environmental (season) and host demographic (age, sex) conditions. This study examines five years of seasonal health and co-infection patterns in African buffalo (Syncerus caffer). We use data on two groups of gastrointestinal parasites, coccidia and nematodes, to test the hypothesis that co-infection and season interact to influence (1) parasite prevalence and intensity and (2) three proxies for host fitness: host pregnancy, host body condition, and parasite aggregation. Our results suggest that season-dependent interactions between nematodes and coccidia affect the distribution of infections. Coccidia prevalence, coccidia intensity and nematode prevalence were sensitive to factors that influence host immunity and exposure (age, sex, and season) but nematode intensity was most strongly predicted by co-infection with coccidia and its interaction with season. The influence of co-infection on host body condition and parasite aggregation occurred in season-dependent manner. Co-infected buffalo in the early wet season were in worse condition, had a less aggregated distribution of nematode parasites, and lower nematode infection intensity than buffalo infected with nematodes alone. We did not detect an effect of infection or co-infection on host pregnancy. These results suggest that demographic and seasonal variation may mediate the effects of parasites, and their interactions, on the distribution and fitness costs of infection.