Seasonal hypoxia [dissolved oxygen (DO)???2 mg?l?1] occurs over large regions of the northwestern Gulf of Mexico continental shelf during the summer months (June–August) as a result of nutrient enrichment from the Mississippi–Atchafalaya River system. We characterized the community structure of mobile fishes and invertebrates (i.e., nekton) in and around the hypoxic zone using 3 years of bottom trawl and hydrographic data. Species richness and total abundance were lowest in anoxic waters (DO???1 mg?l?1) and increased at intermediate DO levels (2–4 mg?l?1). Species were primarily structured as a benthic assemblage dominated by Atlantic croaker (Micropogonias undulatus) and sand and silver seatrout (Cynoscion spp.), and a pelagic assemblage dominated by Atlantic bumper (Chloroscombrus chrysurus). Of the environmental variables examined, bottom DO and distance to the edge of the hypoxic zone were most strongly correlated with assemblage structure, while temperature and depth were important in some years. Hypoxia altered the spatial distribution of both assemblages, but these effects were more severe for the benthic assemblage than for the pelagic assemblage. Brown shrimp, the primary target of the commercial shrimp trawl fishery during the summer, occurred in both assemblages, but was more abundant within the benthic assemblage. Given the similarity of the demersal nekton community described here to that taken as bycatch in the shrimp fishery, our results suggest that hypoxia-induced changes in spatial dynamics have the potential to influence harvest and bycatch interactions in and around the Gulf hypoxic zone.