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Background Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinson's disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms. Methods Eighty-two PD patients and sixty-four controls underwent a series of clinical assessments, including Hamilton Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Visual Analog Scale for Pain, and Scale for Outcomes in PD for Autonomic Symptoms. Plasma 5-HT and 5-HIAA levels were measured by HPLC-ECD. Results PD patients exhibited worse performance on nonmotor symptom scales (all P -values <0.001) and presented lower plasma levels of 5-HT ( P < 0.001) and 5-HIAA ( P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = −0.447, P < 0.001; r = −0.407, P < 0.001, respectively) and pain (r = −0.485, P < 0.001; r = −0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT ( P = 0.01) and 5-HIAA ( P = 0.006) remained significantly associated with depression. Conclusions Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD. [ABSTRACT FROM AUTHOR]