Background: End-stage renal failure is one of the widespread diseases requiring hemodialysis renal replacement therapy. However; patients on maintenance hemodialysis usually suffer from fatigue. A recent growing interest is directed at applying non-pharmacological alongside traditional methods for managing such chronic complaints. Therefore, this study aimed to evaluate the effect of deep breathing exercise training on level of fatigue among maintenance hemodialysis patients. Materials and Method: This study is a randomized quasi-experimental design with parallel groups. One hundred hemodialysis patients participated in the study. They were admitted to the Hemodialysis Department of Alexandria Main University Hospital. The patients were randomly and equally assigned to either the control group or the intervention group (n=50 each). Fatigue was measured in both groups; before and four weeks after nursing intervention using Fatigue Assessment Scale (FAS). Results: Prior to deep breathing exercises, the total mean percent score of fatigue in the intervention group was 66.30±12.19 compared to 62.80±13.12 in the controls. After four weeks of performing the exercise; the mean score was dramatically decreased to 26.25±5.47 in the intervention group compared to 61.40±11.06 in the control. Additionally, a statistically significant difference within the intervention group was declared before and after the intervention (P<0.001). Conclusion: Performing deep breathing exercises for twenty minutes, twice per day for a full month; can reduce maintenance hemodialysis patients’ fatigue level. Key words: Breathing Exercises, Chronic Renal Failure, Maintenance Dialysis, Fatigue, Fatigue Assessment Scale, Nursing intervention.