To assess the risk of pesticide mixtures in lagoon waters, this study adopted a multi-step approach using integrative passive samplers (POCIS) and concentration addition (CA) toxicological models. Two French Mediterranean lagoons (Thau and Or) were monitored for a range of 68 pesticides continuously over a period of a year (2015–16). The findings revealed mixtures of dissolved pesticides with varying composition and levels over the year. The Or site contained more pesticides than Thau site (37 vs 28 different substances), at higher concentrations (0.1–58.6 ng.L−1 at Or vs <0.1–9.9 at Thau) and with overall higher detection frequencies. All samples showed a potential chronic toxicity risk, depending on the composition and concentrations of co-occurring pesticides. In 74 % of the samples, this pesticide risk was driven by a few single substances (ametryn, atrazine, azoxystrobin, carbendazim, chlorotoluron, irgarol, diuron and metolachlor) and certain transformation products (e.g. DPMU and metolachlor OA/ESA). Individually, these were a threat for the three taxa studied (phytoplankton, crustaceans and fish). Yet even a drastic reduction of these drivers alone (up to 5 % of their current concentration) would not eliminate the toxicity risks in 56 % of the Or Lagoon samples, due to pesticide mixtures. The two CA-based approaches used to assess the combined effect of these mixtures, determined chronic potential negative impacts for both lagoons, while no acute risk was highlighted. This risk was seasonal, indicating the importance of monitoring in key periods (summer, winter and spring) to get a more realistic picture of the pesticide threat in lagoon waters. These findings suggest that it is crucial to review the current EU Water Framework Directive's risk-assessment method, as it may incorrectly determine pesticide risk in lagoons.