Purpose: The aim of this study was to evaluate the relationship between illness acceptance, life satisfaction, stress intensity, and their impact on the quality of life (QOL) in patients with multiple sclerosis (MS). Design: Descriptive and correlational study. Methods: A group of 100 patients with MS responded to the Expanded Disability Status Scale, the World Health Organization Quality of Life Brief (WHOQOL-BREF) Scale, the Acceptance of Illness Scale (AIS), the Perceived Stress Scale (PSS-10), the Satisfaction With Life Scale (SWLS), and a sociodemographic questionnaire. Findings: A significant relationship was shown between the mean scores of AIS, SWLS, PSS-10, and WHOQOL-BREF; however, there was no relationship between the mean scores of AIS, SWLS, PSS-10, WHOQOL-BREF and the Expanded Disability Status Scale. Conclusion: Quality of life in patients with MS is positively affected by higher level of disease acceptance and life satisfaction as well as a lower level of perceived stress. Clinical Relevance: Rehabilitation nurses should consider the patient's disease acceptance, QOL, perceived stress, disability level, and satisfaction of life in planning and implementing a comprehensive rehabilitation plan.