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Apalachicola Bay, a river-fed estuary in the northeast Gulf of Mexico is experiencing impacts from anthropogenic and climate-induced changes in freshwater inputs and sea level rise. These synergistic pressures have resulted in a historic oyster fishery collapse and the expansion of mangroves, which are displacing native salt marsh. Understanding how these natural and man-made-driven changes have affected the nekton community is essential for the sustainable management of this coastal region. To evaluate changes in nekton occurrence and distribution in Apalachicola Bay, we analyzed 20 years of biological monitoring data. Our results indicated that spatial variation in species' populations was driven by differences in salinity, while seasonal changes were driven by temperature. Freshwater inflow is the primary driver of salinity, and these differences demonstrated that river flow reductions have the potential to alter nekton communities. The effects of climate-driven droughts and anthropogenic freshwater flow reductions on estuarine community structure highlight the importance of maintaining sufficient river flow for nursery areas, which provide ecosystem services for the region. Ultimately, these findings support the continued need for monitoring programs that track accelerating ecosystem change and provide a clearer understanding for how community composition will respond to global change. [ABSTRACT FROM AUTHOR]