Dams are prone to causing negative effects on downstream ecosystems by their potential to alter riverine water quality. In the case of Itezhi-Tezhi Reservoir (Zambia), a nutrient-poor wetland located downstream is affected by low oxygen concentrations owing to the withdrawal of deep reservoir water and by low nitrogen (N) and phosphorus (P) loads due to reservoir-internal nutrient depletion. We quantified the decrease in oxygen and nutrients by estimating mass balances as well as outflow concentrations by applying a biogeochemical reservoir model. From the mass balances, retention rates of similar to 50% of N and similar to 60% of P inputs were estimated. Hypoxic conditions during similar to 190 d in the outflow may be avoided if 50% of hypolimnetic turbine withdrawal are replaced by epilimnetic water. This optimized scenario yielded five-times higher dissolved N and P output loads. This study presents a generally applicable optimization procedure to minimize effects on downstream water quality.