Most animals are concurrently infected with multiple parasites, and interactions among these parasites may influence both disease dynamics and host fitness. However, the sublethal costs of parasite infections are difficult to measure and the effects of concomitant infections with multiple parasite species on individual physiology and fitness are poorly described for wild hosts. To understand the direct and indirect physiological costs of co-infection, we investigated the relationships among gastrointestinal parasite richness, species identity, and abundance and host hematological parameters, body condition, and investment in lymphocyte defenses. Using aggregate-scale parasite data from African buffalo (Syncerus caffer), we found few direct or indirect associations between infection and hematology in male hosts, and no significant associations were observed in female hosts or with respect to body condition in either sex. These results suggest that only strong physiological effects are detectable with aggregate-scale parasite data, and that hematological variables may be more sensitive to changes in condition than standard body fat condition indices. Analyses accounting for parasite species identity in female buffalo revealed that different parasites show distinct relationships with host hematology, body condition, and immune investment. However, four of six species-specific associations were obscured when parasites were considered in combination. Overall, fitness-related physiological mediators such as hematological indices may provide assessments of direct and indirect effects of parasite infection, particularly when parasite species identity and community composition are considered.