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Electroconvulsive therapy (ECT) is considered one of the most effective treatments for psychiatric disorders. ECT has proven effective in the treatment of depression, mania, catatonia and psychosis. It is presumed that seizures induced during ECT administration cause toxicity and potentially neuronal and glial cell death. A broad range of neurological disorders increase cerebrospinal fluid and serum levels of neuron-specific enolase (NSE) and S-100b protein. This study aims to investigate the effect of ECT on NSE and S-100b levels, which, together, serve as a proxy for neuronal cell damage. Serum concentrations of S-100b and NSE of adult patients who received ECT were measured by immunoluminometric analysis before and after treatment. A two-way ANOVA test was used to estimate the statistical differences in marker concentrations between the subgroups of the study population. Results: A total of 55 patients were included in the analysis: 52.73% (n = 29) were diagnosed with depression, 21.82% (n = 12) with schizophrenia or other psychosis, 16.36% (n = 9) with mania and 9.09% (n = 5) with catatonia. There were no statistically significant changes in NSE (p = 0.288) and S-100b (p = 0.243) levels. We found no evidence that ECT induced neuronal damage based on NSE and S-100b protein levels measured in the serum of patients before and after treatment.