Fibroblast growth factor 19 (FGF19) is a type of gut-derived postprandial hormone. FGF19 plays a key role in coordinating liver bile acid biosynthesis and gallbladder motility and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentrations, and reducing body weight. In the present study, we investigated the presence of FGF19 in human cerebrospinal fluid (CSF) and investigated relationships with a cluster of characteristic emotions and behaviors. Eighty-three male subjects were recruited and participated in the study. The levels of CSF FGF19 were assayed by enzyme-linked immunosorbent assay, and FGF19 levels showed considerable interindividual variations, ranging from 80.54 to 1479.78 pg/ml. Pearson correlation analysis revealed no correlation between CSF FGF19 levels and age or Body Mass Index. Significant correlations were found between CSF FGF19 levels and Pittsburgh Sleep Quality Index scores, Suicide Attitude Questionnaire factors, Barratt Impulsiveness Scale scores, and Beck Depression Inventory scores, and CSF FGF19 levels independently affected Beck Depression Inventory scores. Our findings provide evidence of the presence of FGF19 in human CSF and the role of FGF19 in mood regulation in humans.