Ample historical evidence has demonstrated the neurotoxicity of organic Hg. However, several studies have suggested that Se effectively sequesters MeHg. The affinity of Hg is up to ≈106 times higher for Se molecules than for comparable sulfur molecules, most of which are components of brain enzymes. The neurotoxicity of MeHg is associated with its binding to Se and the resultant interference with selenoenzymes (Ralston & Raymond, Global Advances in Selenium Research from Theory to Application, 2016). Therefore, having ample Se reserves is an effective way to mitigate MeHg’s toxicity. When the molar ratios of Se to Hg in fish exceed 1.0, ingestion of the fish is unlikely to deplete Se reserves. The goal of this study was to determine the Hg and Se levels, and the Se:Hg molar ratios in freshwater fish from south Louisiana and the implications of those ratios with respect to fish consumption and Hg advisories. Five waterbodies were surveyed (University lake, Calcasieu lake, Toledo Bend, the Atchafalaya River and Henderson Lake). The sampled species included black drum (Pogonias cromis), catfish sp., largemouth bass (Micropterus salmoides) and bluegill (Eupomotis macrochirus). All fish were assayed for total Hg and Se. The average Hg concentration was 0.001 µmol g−1 (0.21 ppm), and all concentrations were below the 1 ppm US FDA action level (from 3.1 × 10–5 to 0.003 µmol g−1). Se concentrations exceeded Hg concentrations in most cases. The average Se concentration was 0.003 µmol g−1 (0.27 ppm), all concentrations were around or less than 1.0 ppm (from 3.7 × 10–4 to 0.017 µmol g−1). Hence, the Se:Hg molar ratios were >1 in all fish except largemouth bass from Henderson Lake. In general, Se was detected in sufficient amounts to sequester Hg, but consumption of largemouth bass from Henderson Lake would pose no risk only if anglers followed the posted Hg advisory. For advisory purposes, perhaps, both Hg and Se levels and Se:Hg molar ratios should be considered. In general, the results indicated that risk assessment will require consideration of both the fish species and body of water, because both can influence Se and Hg concentrations and Se:Hg molar ratios.