There has been persistent interest in the mediating role of the micronutrient selenium (Se) in mercury (Hg) toxicity since the 1960s. Despite many unresolved questions regarding Se- Hg interactions, considerable research has been performed to document Se:Hg molar ratios in aquatic animals as a basis for inferring the health risks associated with their consumption. We compiled the co-reported Se and Hg data for 386 shellfish, finfish, and aquatic mammals from 89 papers to assess differences in consumption safety categorizations according to health risk metrics that (a) consider Hg concentrations alone or (b) co-consider Se and Hg concentrations. Species-specific mean Hg concentrations for 23% of all data points in our database exceeded the FAO/ WHO maximum level, and 68% and 83% had estimated daily intake per meal values for adults and children above the Joint FAO/WHO Expert Committee on Food Additives Provisional Tolerable Daily Index. In contrast, only 12% of data points would be categorized as unsafe for consumption on the basis of their 1:1 Se:Hg molar ratios. Se-inclusive risk metrics reversed safety categorizations for a majority of high-trophic level species that are most likely to exceed Hg-based risk thresholds. Adopting Se-inclusive risk metrics has potentially significant implications for seafood consumer health and is likely premature.