Background and aims: Antipsychotic treatment may contribute to low vitamin D levels and have impact on direct anti-inflammatory activity such as adiponectin activity and indirect proinflammatory activity such as leptin and resistin activity.However, vitamin D levels and adipokines mediated effect on weight gain and increased adiposity are not well evaluated. This study, therefore, assessed vitamin D and adipokines-mediated obesity among Ghanaian psychiatric patients.Methods: This comparative cross-sectional study was conducted at psychiatric unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana. Anthropometric measurements, sociodemographic and previous medical history were taken from 300 antipsychotics treatment naïve and active patients. Obesity was classified using World Health Organization (WHO) body mass index (BMI)-specific cut-offs. Blood samples were collected for serum vitamin D and adipokines (adiponectin, leptin, and resistin) analysis using enzyme-linked immunosorbent assay. Statistical analyses were done using SPSS version 26.0 and GraphPad Prism version 8.0. Results:We observed higher prevalence of obesity among treatment active psychiatric patients (40.7%) compared to treatment naïve group (16.8%). Vitamin D insufficiency and deficiency prevalence were significantly higher among the treatment active group (25.3%; 39.5%; p < 0.001) and associated with increased