To evaluate blood serotonin (5-hydroxytryptamine [5-HT]) levels in patients with chronic central serous chorioretinopathy (CSC).A case-controlled retrospective study.Forty-nine patients with CSC and 30 age-matched control subjects.Blood 5-HT levels were measured using high-performance liquid chromatography.Blood 5-HT levels in patients with acute or chronic CSC were measured at the initial visit and compared with those in controls.The blood 5-HT level (98.2±27.5 ng/ml) in patients with chronic CSC was significantly lower than those in patients with acute CSC (122.5±23.9 ng/ml, P = 0.0081) and controls (128.5±35.8 ng/ml, P = 0.0013). After adjusting for covariates, patients with decreased blood 5-HT levels were found to be more likely to develop chronic CSC (odds ratio, 0.97; 95% confidence interval, 0.95-0.99; P = 0.009).These results suggest that serotonin may have a role in chronic CSC pathogenesis and is associated with disease progression.