Aquatic species are important sources of high-quality protein and contribute significantly to global food security and national economies. In Türkiye, the European seabass (Dicentrarchus labrax) accounts for approximately 37% of marine aquaculture production and is widely cultured in coastal farming systems. However, diseases and environmental stressors remain major constraints that can significantly limit production in European seabass (Dicentrarchus labrax) aquaculture. Among these factors, water quality management is one of the most critical parameters affecting fish health and farm productivity. Physical approaches, such as filtration systems and ultraviolet (UV) treatment, are commonly used to maintain water quality; chemical disinfectants, such as ozone and chlorine, are also commonly used as essential complementary strategies. Nevertheless, these agents may be ineffective and can cause undesirable pathological effects in fish. Before the experiment, the 96-h median lethal concentration (LC50) of Chlorine dioxide for European seabass was determined experimentally to be 1.33 mg/L. Based on this value, the present study aimed to evaluate the pathological effects of Chlorine dioxide at different concentrations (0.375, 0.750, 1.125, 1.5, 1.875, and 2.25 mg/L) in various tissues and organs (skin, gills, liver, heart, kidneys, and intestines) of 9-19-month-old European seabass. Fish were exposed to Chlorine dioxide for 7 days under semi-static conditions, with daily renewal of the disinfectant solution. In addition, oxidative stress and apoptosis-related biomarkers were evaluated in liver tissue. Macroscopically, haemorrhages were observed in the gills and liver. Histopathological examinations revealed dose-related pathological alterations, including degeneration, necrosis, and epithelial sloughing in the gills; hepatocyte swelling, vacuolization, and necrosis in the liver; and oedema in the brain. Histopathological changes were scored as 0 in the control group, and scores from 1 to 4 were assigned based on lesion severity. Scoring results for gill and liver tissues indicated that high-dose groups (1.5, 1.875, and 2.25 mg/L) had significantly higher lesion scores compared with the low-dose groups (0.375, 0.75, and 1.125 mg/L), demonstrating a significant increase in tissue damage with increasing dose (p < 0.001, n = 10 per group). ELISA analyses of oxidative stress and apoptosis biomarkers (Caspase-3 (pmol/L), Tumour Necrosis Factor-? (pmol/L), Cytochrome-C (pmol/L), Apo-1/Fas (pmol/L), Malondialdehyde (pmol/L), and P53/Tumour Protein P53 (pmol/L) showed no significant induction of oxidative stress or apoptotic responses in liver tissue following Chlorine dioxide exposure. In several cases, biomarker levels were significantly lower than those of the control group, indicating a suppression or reduction relative to baseline levels rather than activation of these pathways. In conclusion, Chlorine dioxide may be used as a disinfectant in marine aquaculture for European seabass at concentrations between 0.750 and 1.125 mg/L for short-term applications. Under the experimental conditions of this study, these concentrations did not induce significant oxidative stress or apoptosis, although dose-dependent histopathological alterations were observed at higher exposure levels.