© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Rivers are critical ecosystems for protecting and harboring high biodiversity. Tropical rivers particularly are unique for facing extreme climatic events under the current accelerated disruption from human activities. The Bobos-Nautla river basin is exposed to climatic events and disturbances from anthropogenic impacts that stress aquatic organisms. We assessed the health condition of this river system using a non-conventional biomonitor, Corydalus sp., with a set of early-warning biomarkers including lipid peroxidation levels (LPO) and antioxidant activity, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the neurotransmitter acetylcholinesterase (AChE) considering their spatial and temporal variations. Biomarkers and water quality parameters were analyzed, and the integrated biomarker response (IBR) was assessed as a stress index. Biomarkers showed no significant spatial differences; however, a high-stress period during the rainy season was detected, evidenced by the highest LPO levels; this period is related to the leaching of allochthonous materials from agricultural and urban zones. The peak IBR value during the rainy season confirmed the seasonality of biomarkers. A slight increase in IBR was recorded in lowlands, seemingly associated with agricultural land and human settlements. A principal component analysis showed nutrient enrichment during the rainy season and depletion during the cold-dry season, together with a peak activity of antioxidant enzymes. These results highlight the importance of climatic events such as the rainy season on the health condition of Corydalus sp., which is highly sensitive to the complex mixtures of pollutants that enter the waterbody during extreme climatic events, promoting oxidative stress. Our results also showed the ability of Corydalus sp. to recover and return to a basal level.