The majority of Louisiana’s wild crayfish landings are harvested from the Atchafalaya River Basin (ARB) during floodplain inundation from the annual flood pulse. Spatial and temporal heterogeneity in ARB physicochemical characteristics are associated with flood pulse characteristics and floodplain inundation, and extensive areas of the ARB experience environmental hypoxia (dissolved oxygen [DO] < 2.0 mg·L-1) for several weeks to months during the annual flood pulse. The purpose of this research was to evaluate the effects of flood pulse characteristics and physicochemistry on harvested crayfish populations at 14 sites in the ARB that were sampled biweekly during the 2016 and 2017 crayfish seasons. Despite dissimilar 2016 and 2017 flood pulse characteristics, red swamp crawfish Procambarus clarkii and southern white river crawfish P. zonangulus carapace length and CPUE were similar between sample years. Comparisons of P. clarkii populations among physicochemical location groupings indicated that DO concentration, particularly chronically hypoxic water, is the principal abiotic variable influencing P. clarkii population characteristics. Although not significant, normoxic locations produced larger crayfish and yielded higher CPUE values for the majority of both crayfish seasons. Furthermore, hemolymph protein concentrations in P. clarkii from normoxic areas were significantly and consistently higher than individuals from chronically hypoxic locations.