Musculoskeletal Disorders (MSDs) are disorders or damage the muscular and skeletal systems of the human body caused by an imbalance of workload on the capabilities of the muscles and skeleton which significantly directly or indirectly reduce work productivity. Workload can be divided into two, which are physical workload and mental workload which tends to lead to the burden received by an employee in a job. This study aimed to analyze the effects of physical workload, mental workload and work posture towards fatigue on Musculoskeletal Disorders in employees at PT. Nusantara Plantation XIV. This type of research was an analytic observational with a cross sectional research design. The sample used the non-probability sampling method with a sample of 118 respondents. The data collection instruments included an oxymeter, reaction speed, Rapid Entire Body Assessment (REBA), Nordic Body Map and NASA-TLX questionnaires, interviews and observations. The data analysis used in this study was the path analysis. There was a direct effect of work posture on fatigue (p=0.000). Physical workload on fatigue (p=0.038). Mental workload on fatigue (p=0.004). Work posture towards MSDs (p=0.533). Physical workload on MSDs (p=0.188). Mental workload on MSDs (p=0.000). There was an indirect effect of work posture on MSDs through fatigue (p=0.020). The work posture and physical workload did not have a direct effect on musculoskeletal disorders, while work posture, physical workload and mental workload had a direct effect on fatigue and musculoskeletal disorders and there was an indirect effect of work posture on musculoskeletal disorders through fatigue.