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Stress is a risk factor for central serous chorioretinopathy (CSC), but a suitable biomarker of this stress has not been identified. We aimed to evaluate alpha-klotho (αKl) as a potential biomarker of CSC. The circulating concentrations of αKl in patients diagnosed with acute or chronic CSC and treated at Hyogo College of Medicine between December 2019 and July 2021 were retrospectively compared with those of healthy individuals. We also compared the αKl concentrations of patients with acute or chronic CSC. Furthermore, we evaluated the relationships of age, sex, smoking status, and subfoveal choroidal thickness (SFCT) with αKl concentration. Patients in whom subretinal fluid reaccumulated in the same eye after its resolution were defined as having recurrent CSC. We studied 56 patients (46 men and 10 women) and 27 healthy controls (19 men and 8 women); and 38 and 18 eyes with acute and chronic CSC, respectively. The mean circulating concentration of αKl was higher in patients with CSC than in controls (827±232 and 724±183 pg/mL, respectively; p = 0.035). The mean SFCT was greater in patients with CSC than in controls (416±91.0 and 278±96.3 μm, respectively; p<0.0001). The mean αKl concentration was significantly higher in the patients with acute CSC than in those with chronic CSC (898±221 and 740±224 pg/mL, respectively; p = 0.038). Recurrence of CSC occurred in 10 of 56 (17.9%) eyes, of which five eyes were in the acute CSC group and five were in the chronic CSC group. Patients who experienced recurrence had significantly higher αKI concentrations than those who did not (p = 0.0219). There were no significant relationships of αKl concentration with age, sex, smoking history, or SFCT. In summary, the circulating αKI concentrations of patients with CSC are high, which suggests that αKI may be an indicator of stress in such patients.