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We compared the effect of Xymedon (100 mg/kg), Mexidol (50 mg/kg), and their combination on spermatogenesis indicators and functional state of spermatozoa in rats with Walker-256 carcinoma treated with doxorubicin (4 mg/kg) and cyclophosphamide (45 mg/kg) (once intraperitoneally on day 11 after tumor cells transplantation). Xymedon and Mexidol were injected intramuscularly for 10 days starting from day 11 of the experiment. The studied parameters were evaluated on experimental days 14 and 21. We have established that gonadoprotective effect of Xymedon developed gradually and persisted longer than that of Mexidol. It manifested in an increase in the number of epithelial spermatogenesis cells (spermatogonia by 3.2 times, early spermatids by 2.2 times, late spermatids by 2.9 times, and Leydig cells by 4 times) in the testes and also the proportion of viable progressively and non-progressively motile epididymal spermatozoa (by 2 times). The combination of Xymedon and Mexidol stimulated spermatogenesis (with restoration of the initial level of spermatocytes, an increase in the number of early spermatids by 65.5 and 99% in comparison with Xymedon alone and Mexidol alone, respectively) and increased the number of viable epididymal spermatozoa more effectively than Xymedon and Mexidol alone by 54 and 60%, respectively., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)