Combined sewer overflows (CSO) after heavy rainfall can cause acute depletions of dissolved oxygen (DO) in the Berlin River Spree. Further aggravation of ecological deficits can be expected from global climate change. A planning instrument for CSO impact assessment under different sewer management and climate conditions has been developed at Kompetenzzentrum Wasser Berlin. It couples the sewer model InfoWorks CS, the river water quality model Hydrax/QSim and an impact assessment tool. The planning instrument was validated for the years 2010 and 2011. Simulation results for the critical parameters discharge and DO concentrations in the Berlin River Spree agree well with measurements. Although not all observed DO deficits can be simulated accurately, the very good representation of processes related to the oxygen budget allows assessing relative changes in boundary conditions, e.g. from climate change or different CSO control strategies. The conducted scenario analysis indicates that the coupled sewer-rivermodel reacts sensitively to changes in boundary conditions (temperature, rainfall, storage volume and other CSO control strategies, etc.). Based on the simulation year 2007 – representing an extreme year with regards to CSO volume and critical conditions in the river – sewer rehabilitation measures planned to be implemented until 2020 are predicted to reduce total CSO volumes by 17% and discharged pollutant loads by 21 - 31%. The frequency of critical DO conditions for the most sensitive local fish species will decrease by one third. For a further improvement of water quality after the year 2020, the reduction of impervious surfaces emerges as a very effective management strategy where feasible. A reduction of the impervious connected area by 20% results in a decrease in the frequency of critical DO conditions by another third. The studied increase in surface air and water temperature as part of the climate change scenarios leads to a significant aggravation of DO stress due to background pollution in the Berlin River Spree, while acute DO depletions after CSO are barely affected. However, changes in rain intensity have a considerable effect on CSO volumes, pollutant loads and the frequency of critical DO concentrations. A general reduction of discharged pollutant loads by 60% based on the sewer status 2020 can prevent critical DO conditions in the Berlin River Spree, even for the exceptionally rain intense year 2007. A detailed analysis of river processes after CSO, has shown that the biodegradation of organic carbon compounds is the most important contributor to acute DO depletions in the Berlin River Spree. An additional impairment of DO conditions is caused by the inflow of oxygen free CSO spill water and suspended solids into the Berlin River Spree. In this report, CSO impacts under different management strategies or climate change conditions are assessed only for a part of the Berlin combined sewer system (although the main part) and for one exemplary year. An extension of the planning instrument to the entire combined sewer system would enable to evaluate the full impact of measures. For a robust prediction of future CSO impacts it is also recommended to test different simulation periods or conduct long-term simulations.