The urban stretch of the River Spree is a regulated lowland-river, which is affected by a number of anthropogenic pressures, most notably impacts from combined sewer overflows (CSO) of the Berlin sewer system. Collected data show that occurrence of CSO can be detected in the river through a combination of continuous monitoring data, such as specific conductivity, ammonium (NH4), chemical oxygen demand and dissolved oxygen (DO). Comparison with stormwater guidelines indicates that drops in DO from CSO lead to regular problematic conditions for the fish fauna. In contrast, observed NH4 peaks never reach fish-toxic levels. Mitigation measures are currently implemented to reduce these negative impacts during storm events. The effect of past and potential future CSO measures can be studied with a model tool, which has been tested and is currently calibrated based on the above monitoring data.