Background: Patients undergoing hemodialysis with end stage renal disease (ESRD) experiences many complications. Fatigue and sleep are the most common problems faced by them and there is a need for an effective intervention to minimize these complications. Objective: The purpose of this study was to assess the effectiveness of progressive muscle relaxation on fatigue and sleep quality of patients undergoing hemodialysis with ESRD. Jacobson’s progressive muscle relaxation (JPMR) is a relaxation technique on the skeletal muscles by giving the sensation of tension in a skeletal muscle group and then to focus on getting the sense of relaxation. Methods: It is a quasi-experimental non-equivalent control group pre-test – post-test design. A total of 100 samples were selected for the study using purposive sampling technique and they were assigned to two groups namely group I with 50 samples who received JPMR therapy and group II the control group with 50 samples who received routine treatment of the dialysis unit. Outcome variables measured were fatigue and sleep quality on 1st week before intervention, end of 4th week and at the end of 8th week after the intervention. Demographic variables, Revised Piper Fatigue Scale and Pittsburgh Sleep quality Index were used to measure the outcome variables. Statistical analysis was done using the chi-square test, Student t- test, repeated measures ANOVA, F- test and Karl Pearson's correlation coefficient test. Results: The findings showed that there was a significant reduction in fatigue score (F=562.33, p=0.001) and improvement in the sleep quality score (F=327.66, p=0.001) in the progressive muscle relaxation group while comparing to the control group. Conclusions: It can be concluded that JPMR therapy had a positive effect in reducing the fatigue and improving the sleep quality of patients undergoing hemodialysis with ESRD.