Long-lived species are often predicted to be buffered against seasonal variation: longevity means low annual mortality and reproductive rates and annual variability in climate may therefore have a smaller impact on population growth rates of long-lived species in comparison to short-lived ones. However, little is known of the physiological mechanisms underlying such patterns in long-lived species. In this study, we investigated seasonal variation in the health of Asian elephants living in a seasonal monsoon climate. We used two complementary methods: (i) global and (ii) trait-by-trait analyses of seasonal effects on 23 health parameters of 225 individually marked elephants with known age and reproductive and health history, with repeated measures per individual over a 26-month period. The global analysis highlighted the biggest differences in health between the hot and monsoon seasons. Our trait-specific analyses identified the physiological functions underlying such health variation in different ecological settings, including haematological, immunological, muscular, kidney and liver functions, as well as protein balance and electrolytes. Overall, the results suggest that even long-lived, large mammals may experience physiological changes in response to seasonal variation that in extreme circumstances can pose a significant health risk.