Aim The present study aimed to explore the circadian rhythm of salivary serotonin in patients with major depressive disorder before and after treatment with fluoxetine and its relationship with clinical therapeutic effect.Methods This study investigated salivary serotonin in 13 outpatients with major depressive disorder and age-and sex-matched healthy controls.Depressed patients received six weeks fluoxetine treatment (20 mg/d),saliva was collected before and four weeks after treatment.A total of 8 time-point salivary serotonin was measured across the whole day.Multioscillator cosinor model was used to fit the rhythms.Results Serotonin concentration in saliva ranged from 0.32 ng/mL to 9.62 ng/mL.