Background and Objectives: Disability and intolerance to exercise are common in heart failure and can lead to feelings of fatigue in patients and can change patients’ lifestyles; therefore, this study was performed to Evaluation of physical activity in patients with heart failure and its relationship with fatigue. Methods: In this descriptive cross-sectional study, 100 patients with heart failure referred to rehabilitation centers in southeastern Iran were selected by convenience sampling. Data collection tools were RAPA physical activity questionnaire and FACIT fatigue questionnaire. Data were analyzed using Spearman correlation coefficient and regression. Significance was considered 0.05. Results: The results showed that the mean±sd of physical activity was 2.59‌±1.33 and the mean±sd of fatigue in the samples was 20.27±6.11 and the majority of patients had below normal physical activity and fatigue was unfavorable in the majority of them. The total score of physical activity was inversely and significantly correlated with the total score of fatigue. The results showed that 30.6% of the changes in patients ‘fatigue were influenced by variables of drug use, history of heart surgery and the degree of disease and they were predictors of patients’ fatigue. Conclusion: The results of the present study showed that patients who were more physically active had less fatigue. Due to the fact that fatigue is very common in patients with heart failure, it is recommended to take the necessary interventions to increase patients’ knowledge and skills about physical activity, to reduce the fatigue of patients