Background <p>Multiple sclerosis (MS) is becoming more prevalent. Physical impairments and sleep issues, particularly fatigue, diminish these patients’ quality of life. One of the most successful and long-lasting strategies for managing symptoms is patient education. The aim of this study was to evaluate effect of a nurse-led online support program on fatigue, sleep, and quality of life in patients with multiple sclerosis (PwMS).</p> Methods <p>This quasi-experimental study was conducted in the MS outpatient clinic of a university hospital in Istanbul. Patients participated in a five-week nurse-led online support program and were assessed using the Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), and EQ-5D Quality of Life Scale before, after, and at 3 and 6&#xa0;months. Patients’ step counts were also recorded.</p> Results <p>Thirty patients who completed the program were included in the study. Compared to baseline, FSS scores and number of steps improved (<i>p</i> = 0.008, <i>p</i> = 0.008). PSQI scores also improved (<i>p</i> = 0.026). Although there was no difference in EQ-5D symptom scores, the EQ-5D visual analogue scale scores tended to improve (<i>p</i> = 0.085).</p> Conclusions <p>A nurse-led online support program may be a feasible and resource-efficient approach to managing fatigue and sleep disturbances in PwMS, especially in settings with limited access to care. Larger controlled studies are needed to confirm these findings.</p> Trial registration <p>This study was registered on ClinicalTrials.gov on August 24, 2023 (NCT06166043).</p>