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More than 95% of the water in the South Platte River downstream from the largest wastewater treatment plant serving the metropolitan Denver, Colorado, area consists of treated effluent during some periods of low flow. Fluctuations in effluent-discharge rates caused daily changes in river stage that promoted exchange of water between the river and bottom sediments. Groundwater discharge measurements indicated fluxes of water across the sediment-water interface as high as 18 m3 s−1 km−1. Laboratory experiments indicated that downward movement of surface water through bottom sediments at velocities comparable to those measured in the field (median rate ≈0.005 cm s−1) substantially increased dissolved oxygen uptake rates in bottom sediments (maximum rate 212 ± 10 μmol O2 L−1 h−1) compared with rates obtained when no vertical advective flux was generated (maximum rate 25 ± 8.8 μmol O2 L−1 h−1). Additions of dissolved ammonium to surface waters generally increased dissolved oxygen uptake rates relative to rates measured in experiments without ammonium. However, the magnitude of the advective flux through bottom sediments had a greater effect on dissolved oxygen uptake rates than did the availability of ammonium. Results from this study indicated that efforts to improve dissolved oxygen dynamics in effluent-dominated rivers might include stabilizing daily fluctuations in river stage.