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The paper reports results of four intensive campaigns carried out on the Seveso River (Milan metropolitan area, Italy) between 2014 and 2016, during intense precipitation events. Laboratory analyses were coupled with on-site, continuous measurements to assess the impact of pollutants on water quality based on both conventional and surrogate parameters. Laboratory data included total suspended solids, caffeine, total phosphorus and nitrogen, and their dissolved forms. Screening of trace metals (Cr, Cu, Pb, Ni, Cd) and PBDEs (polybromodiphenylethers) was carried out. Continuous measurements included water level, physico-chemical variables and turbidity. Nutrient concentrations were generally high (e.g. average total phosphorus > 1,000 μg/L) indicating strong sewage contributions. Among monitored pollutants Cr, Cu, Pb, and Cd concentrations were well correlated to TSS, turbidity and discharge, being bound mostly to suspended particulate matter. A different behavior was found for Ni, that showed an early peak occurring before the flow peak, as a result of first flush events. PBDEs correlated well to nutrient concentrations, showing the highest peaks soon after activation of the combined sewer overflows, likely because of its accumulation in sewers. In addition to showing the existing correlations between quality parameters, the paper highlights the importance of surrogate parameters as indicators of anthropic pollution inputs.