BACKGROUND: Pentavalent antimonial has been a drug of choice against leishmaniasis, despite the emergence of treatment failure. Identification of resistance markers is urgently needed to design new therapeutic strategies. Iron-Superoxide dismutases (Fe-SODs) are antioxidant enzymes contributing to detoxify reactive oxygen species to prevent a cell from oxidative stress. Since antimonial compounds induce oxidative stress, in this survey, the expression of genes was investigated to identify their expression pattern in clinical resistant isolates. METHODS: This cross-sectional survey was done in Mashhad City, northeast of Iran during 2014 to 2019. The RNA expression level of mitochondrial () and glycosomal () superoxide dismutase was investigated in 25 antimony responsive (n=15) and unresponsive (n=10) anthroponotic cutaneous leishmaniasis (ACL) patients. Total RNA extraction and cDNA synthesis, the qRT-PCR approach was utilized to investigate the relative RNA expression level. RESULTS: The transcript level of s was over-expressed in the most resistant isolates. Gene expression analysis demonstrated the over-expression of and B by a factor of 3.8 and 4.81, respectively, in resistance isolates vs. sensitive ones. CONCLUSION: Aberrant expression of in unresponsive parasites could potentially implicate in detoxifying antimony-induced oxidative stress. Moreover, s might be considered as potential predictive markers of the response to antimonials in ACL patients in endemic areas.