Objectives The dominant evolutionary perspective on adipose tissue has considered it a relatively inert energy store. However, variability in adipose tissue distribution has recently been associated with age, parity, thermal environment and immune function. Genes regulating the innate immune system are more strongly expressed in deep‐lying than peripheral adipose tissue. We hypothesized that central adiposity would correlate more strongly than peripheral adiposity with pathogen load across populations. Methods Primary outcomes were subscapular and triceps skinfolds from 133 male and 106 female populations. National values for disability‐adjusted life years lost, attributable to infectious diseases, were used to index pathogen load. Linear mixed‐effects models were fitted, including a random effect term by country to investigate the association of each skinfold with pathogen load, adjusting for the other skinfold, mean annual temperature and clustering of the populations across countries. Results Adjusting for subscapular skinfold, triceps skinfold was not associated with pathogen load in either sex. Adjusting for triceps skinfold, subscapular skinfold was negatively associated with pathogen load in both sexes (P < 0.02). These associations were independent of variability in annual temperature. Adjusting for pathogen load and temperature, Oceanic populations had a different fat distribution compared to other populations. Conclusions Across populations, higher pathogen load was associated with reduced central but not peripheral skinfolds, supporting the hypothesis that central adiposity is more closely associated with immune function. This scenario might explain why some populations increase disproportionately in central adiposity when the environment shifts from low‐energy high‐pathogen status to high‐energy low‐pathogen status. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.