Multiple Sclerosis (MS) is a chronic progressive inflammatory disease of the Central Nervous System (CNS) and represents the major cause of non-traumatic disability in young adults. Fatigue is one of the most frequent complaints in patients with multiple sclerosis (MS), with a significant impact on the self-care. Energy conservation strategies are one of the key interventions for fatigue management in multiple sclerosis. Aim: This study aimed to evaluate the effect of energy conservation instructions on fatigue and self-care practices among patients with multiple sclerosis. Design: A quasi-experimental research design (pre/post-test control group design) was used to achieve the aim of the study. Hypotheses: H1: Post total mean score of fatigue degree among patients who receive instructions about energy conservation strategies will be lower than the post total mean score of fatigue degree among patients who receive routine hospital care among patients with multiple sclerosis. H2: Post total mean score of self-care practices among patients who receive instructions about energy conservation will be higher than the post total mean score of self- care practices among patients who receive routine hospital care among patients with multiple sclerosis. Sample: A convenient sample of female adult patients divided randomly into energy conservation and control groups for not less than 60 patients, 30 patients assigned for each group. Data collection tools: Three tools were used to collect data: (1) Personal and Medical Data Form (PMDF), (2) Global Fatigue Index (GFI), (3) Appraisal of Self-care Agency Revised (ASA-R). Results: There was a statistically significant difference in the mean score of fatigue as well as self-care agency among the study group that received energy conservation sessions when compared with the control group that received routine hospital care. Conclusion: Energy conservation strategies could be effective in decreasing fatigue level and increasing the capacity for self-care agency. Recommendations: The energy conservation instructions should be applied for the patients with MS in the early course of the disease to have a maximum benefit.