The monitoring of organic contaminants in the environment has gained tremendous traction in recent times, however, little attention has focused on the development of appropriate methods for the analysis of biological tissues from key sentinel species. In this study, a rapid, low-cost method is presented for the analysis of organochlorine pesticides (OCPs) in fatty biological tissues using a modified QuEChERS (Quick, Easy, Cheap, Efficient, Rugged and Safe) approach. The adapted extraction procedure is tested on biological samples of varying fat content, including fish muscle tissue and two previously untested matrices; coral and adipose tissue. Residue analyses were conducted by two-dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-TOF-MS). The method was fully validated through the evaluation of recoveries, limits of detection, linearity and precision. Mean recoveries (n = 3) for all 18 target compounds ranged between 69 and 102% across all matrices, with relative standard deviations (RSD) <10% in most cases. Limits of detection (LOD) ranged from 0.1 to 2.0 ng g-1. The method was successfully applied to the analysis of real samples collected from iSimangaliso Wetland Park World Heritage Site, South Africa.