Technical Abstract: Degraded streams draining low-relief, intensively cultivated watersheds may experience periods of hypoxia or anoxia. A three-year study of water quality, fish, and physical habitat in the Big Sunflower River in northwestern Mississippi coupled with continuously logged water quality and hydrology data provided by others showed prolonged periods of hypoxia associated with higher flows. Fish species richness was directly related to dissolved oxygen concentration (DO) (r2 = 0.35, p = 0.00004), and ordination using nonmetric multidimensional scaling indicated strong association between fish community structure and DO. Low-head weirs supported relatively dense and diverse fish assemblages and thus provided local habitat enhancement, but may create stagnant zones upstream due to backwater effects that exacerbate low DO problems. Although hypoxia has been reported for some lightly-degraded rivers and floodplains, our observations suggest hypoxia in Big Sunflower River and similar systems alters fish species composition and should be remediated. Cost effective remediation will require better understanding of autotrophic and heterotrophic processes that control DO and the relationship of these processes to discharge.