The present study examined the bioacessibility of DDTs and PBDEs in cooked fish (yellow grouper; Epinephelus awoara) with and without heating using the colon extended physiologically based extraction test. The bioaccessibility of DDTs and PBDEs increased from 60 and 26% in raw fish to 83 and 63%, respectively, after the addition of oil to raw fish. However, they decreased from 83 to 66% and from 63 to 40%, respectively, when oil-added fish were cooked. Human health risk assessment based on bioaccessible concentrations of DDTs and PBDEs in fish showed that the maximum allowable daily fish consumption rates decreased from 25, 59, and 86 g day to 22, 53, and 77 g day for children, youths, and adults, respectively, after fish were cooked with oil. These findings indicated that the significance of cooking oil to the bioaccessibility of DDTs and PBDEs in food should be considered in assessments of human health risk.