The concentrations of seventeen endocrine disruptor compounds (EDCs) that included oestrogens, phytoestrogens, sitosterol, and banned industrial pollutants were investigated at ten sites of the Douro River estuary. Surface waters were collected during 2019. After evaluating the physicochemical data (ammonia, nitrates, nitrites and phosphates), the waters were filtrated and submitted to ... [Show full abstract] solid-phase extraction (SPE) to extract and pre-concentrate (4000-fold) the EDCs. The extracts were derivatized with BSTFA + 1% TMS and analysed by gas chromatography-mass spectrometry (GC-MS). All EDCs showed a high detection rate (97%, on average), exhibiting ubiquity in this estuary. The finding of biologically relevant amounts of oestrogens (up to 8.5 ng/L for oestradiol, E2), phytoestrogens (up to 827 ng/L for biochanin A, BIO-A) and industrial pollutants (up to 2.7 µg/L for nonylphenol di-ethoxylated, NP2EO) strongly support ongoing risks of endocrine disruption for the local aquatic wildlife. Globally, there was an E2-equivalents (E2-EQs) concentration of 25 ng/L and a hazard index (HI) of 26, which further indicates considerable potential for adverse effects on local biota. Moreover, the physicochemical data suggest direct sewage discharges. Beyond possible toxicological effects on fauna, the detected contaminants may pose risks to humans via direct contact (bathing at local fluvial beaches) or by ingestion (local fish).