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Objectives: To assess the prevalence of depression, anxiety and quality of sleep and their relation to increased fatigue scores among patients on chronic hemodialysis. Background: Fatigue is one of the most common endured symptoms by hemodialysis patients, it’s usually unrecognized, untreated and remains complex phenomenon, factors may be attributed to fatigue include demographic, psychological, physiological factors, sleep disorders and dialysis inadequacy. Methods: A cross-sectional study was conducted on 82 patients receiving maintenance hemodialysis at Menoufia University Hospitals from November 2022 till December 2023, Demographic, clinical, laboratory data and clinical questionnaires were recorded for each patient. Results: Prevalence of fatigue, depression, anxiety and poor sleep quality among studied participants was 50%, 73.2%, 82.9% and 86.6% respectively. Ferritin, iPTH, hypovitaminosis D, poor sleep quality, depression and anxiety were the predictors of fatigue in chronic hemodialysis patients. Conclusion: Modifiable predictors of fatigue like higher levels of ferritin, iPTH and low vitamin D and poor sleep quality, depression and anxiety can be optimized that may help to improve fatigue and quality of life of dialysis patients, that is a step towards optimum dialysis.