Background: Pesticide is a cheap and effective substance to eradicate pests, yet it has chronic effects, it causes neuropsychiatric disorders. Neuropsychiatric disorders are associated with affecttive, cognitive, and behavioral disorders. This study aims to analyze the effects of pesticide exposure and psychosocial determinants on neuropsychiatric disorders (depression and anxiety). Subjects and Method: This was a retrospective cohort study conducted in Sukoharjo, Central Java, Indonesia. A sample of 200 rice farmers was selected by fixed exposure sampling. The dependent variable was depression nd anxiety. The independent variables were organophosphate pesticide exposure and psychosocial factors. The neuropsychiatric disorders were measured using DASS-42 questionnaires. The data were analyzed by path analysis. Results: Depression and anxiety were directly increased by high work stress (b= 0.29; 95% CI= 0.19 to 0.38; p< 0.001), depression history of family members (b= 5.71; 95% CI= 3.16 to 8.26; p<0.001), grief and loss (b= 3.21; 95% CI= 0.99 to 5.42; p= 0.005), and past trauma (b= 4.08; 95% CI= 1.81 to 6.34; p<0.001). Depression and anxiety were indirectly affected by the organophosphate pesticide exposure, age through the use of personal protective equipment (PPE), and latest education through the use of PPE. Conclusion: Depression and anxiety are directly increased by high work stress, depression history of family members, grief and loss, and past trauma. Depression and anxiety are indirectly affected by the organophosphate pesticide exposure, age through the use of personal protective equipment (PPE), and latest education through the use of PPE.