PURPOSE: Sleep difficulties are common in patients with multiple sclerosis (MS), which may increase feelings of fatigue, negatively interfere with daily activities, and consequently reduce their quality of life. Studies examining the effects of sleep-targeted interventions in MS are currently limited in the literature. Therefore, we aim to assess the effects of occupational therapy interventions on sleep quality, fatigue, and quality of life in patients with MS. PATIENTS AND METHODS: In a single-blind, randomized, controlled trial, which occurred between April 2018 and March 2019 in Tehran, Iran, 20 eligible patients with MS were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS), and Short-Form Health Survey (SF-36). Patients were allocated randomly into the two following groups: patients receiving care-as-usual for MS (CAU) and patients receiving care-as-usual plus intervention (CAU + intervention). Both intervention groups underwent 2-3 sessions per week lasting 30-45 minutes for 8 weeks and received follow-up assessments. Data were analyzed using independent sample t-tests and Mann-Whitney U tests using SPSS (16 ver.) statistical software. RESULTS: In the intervention group, sleep quality improved significantly across all items (p<0.001, effect size = 0.60) except for sleep efficiency and the use of sleep medications. FSS and FIS in the sleep intervention group were significantly reduced (p<0.001, effect size = 0.76 and p<0.001, effect size = 0.82, respectively). The quality of life in the intervention group improved significantly (p<0.004, effect size = 0.51-0.76) with the exception of the social functioning subgroup. CONCLUSION: Although this is the result of a pilot study and more patients should be added, this intervention program demonstrates improvement in sleep quality and quality of life while decreasing fatigue in patients with MS. Adjunction of this program, if results are similar with more patients, to routine occupational therapy (OT) interventions can help improve the rehabilitation program of MS patients.