Effluents from wastewater treatment plants (WWTP) are point sources of organic matter, nutrients, and emergent pollutants that reduce water quality and alter river ecology at reach scale. In Mediterranean regions, this impact is especially noticeable in summer, when rivers have a low capacity to dilute inputs from WWTP effluents. As water scarcity in these regions increases in intensity and frequency, it is expected that WWTP inputs will gain relevance in determining water availability and quality not only at reach scale, but also at the river network scale. We took advantage of the extreme drought of summer 2022 to assess the impact of WWTP inputs to river flow and nutrient loads in the Besòs river, which drains a large catchment (1038 Km2) highly urbanised (2 million people) in north of Barcelona, Spain. To do so, we conducted a synoptic survey during which we sampled upstream and downstream sites from 22 WWTPs located along the river, from headwaters to the river mouth. River flow was highly fragmented along the river network, with WWTP inputs being the main water source by contributing up to 90% to river flow. Total inflows from WWTPs exceeded the flow measured at the river mouth, indicating that water was intensively used or lost along the river network. Further, the WWTP effluent inputs led to increases in stream nutrient loads, which were higher at the headwater sites. Stream nutrient concentrations decreased downstream from each WWTP effluent input, highlighting that the bioreactivity of this highly humanised river network can contribute to buffer the impact of these point sources and improve water quality. Our results provide empirical support that river restoration management favouring reaches with high nutrient retention capacity can contribute to the good quality of freshwater resources for human use in river networks under a water scarcity context