Biologically significant concentrations of organochlorine pesticides (OCPs) continue to be reported in wildlife populations and are of particular concern in species that occupy the highest trophic levels. Nile crocodiles (Crocodylus niloticus) are important apex predators occurring throughout much of tropical and subtropical sub-Saharan Africa, where they inhabit estuarine and freshwater habitats often impacted by contamination. In this study we examined pesticide residue accumulation in fat tissue from Nile crocodiles at Lake St Lucia, South Africa, where historically large quantities of OCPs have been used for agriculture and disease control. During 2019, we collected tail fat samples from wild (n = 21) and captive (n = 3) individuals to examine the influence of habitat, body size and sex on variations in bioaccumulation. The principal contaminant found was p,p'-DDE, a major persistent metabolite of DDT, which continues to be used in the region for combating malaria. Tissue p,p'-DDE concentrations in wild crocodiles (95-1200 ng g ww) were significantly (p < 0.05) higher compared to captive individuals (23-68 ng g ww) and strongly correlated (R > 0.70) to body length. Male (n = 14) and female (n = 7) wild crocodiles exhibited similar contaminant body burdens, however, total concentrations were substantially lower than those measured in the same population during 2016/2017. Marked differences in residue levels and profiles appear to reflect changes in food availability and dietary exposure associated with a shift in environmental conditions. These findings suggest that periods of environmental stress may be associated with enhanced toxicological risk in crocodiles. Additional work is needed to better understand contaminant accumulation and elimination mechanisms in crocodiles, and their potential effects on reproductive health.