Our aim was to evaluate SESN2 levels in patients with uterine leiomyomas by comparing serum SESN2 levels in myoma patients with the levels in healthy women to deepen our understanding of the pathophysiology of uterine leiomyomas. Patients 18–50 years of age who applied to the University of Health Sciences Turkey, Istanbul Kanuni Sultan Suleyman Training and Research Hospital between January and March 2021 and who were diagnosed with uterine leiomyoma were defined as the ‘myoma group’. The control group included patients without any sign of leiomyomas in routine ultrasonography. The patients’ demographic features, gynecological symptoms, myoma volume and classification were recorded. Serum SESN2 concentrations in venous blood samples were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The study included 31 patients in the myoma group and 30 in the control group. The mean age/gravid/parity or BMI values did not differ significantly between the groups. The only gynecological symptom that showed a significant difference was menorrhagia. Serum SESN2 levels were significantly higher in the myoma group then the control groups (11.7 ± 2.5) (p < 0.001). In conclusion, although uterine leiomyoma is the most common benign tumour in women of reproductive age, there are no known markers for predicting the development of leiomyomas. Based on the results of the current study, SESN2 could be such a marker. IMPACT STATEMENT What is already known on this subject? Uterine leiomyoma is the most common type of benign tumour in women of reproductive age as well as the most common indication for a hysterectomy. Symptoms associated with uterine leiomyoma include abnormal bleeding, chronic pelvic pain, menorrhagia, dysmenorrhoea, dyspareunia and anaemia, which adversely affect the patient’s quality of life. Sestrins are a family of metabolic regulator proteins that play a potential role in carcinogenesis. What the results of this study add? This is the first study evaluating the role of sestrin in the development of uterine leiomyomas. Significantly higher levels of sestrin 2 (SESN2) were detected in patients with leiomyomas. What are the implications of these findings for clinical practice and/or further research? Although uterine leiomyoma is the most common type of benign tumour in women of reproductive age, there are still many unknowns regarding its pathophysiology. Further, there are still no known markers for predicting the development of leiomyomas. Hence, primary prevention is not possible. Based on the results of the current study SESN2, could be such a marker. Further studies are needed to confirm the results of this study.