Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS) with significant impact on daily life. The aim of this study is to explore the association among MS fatigue, clinical disability and depression. Fifty-seven patients were assessed by fatigue severity scale (FSS), expanded disability status scale (EDSS) and Beck depression inventory (BDI). Mean FSS score was 4.1 +/- 1.6. Based on FSS scores, patients were divided into three groups: Patients with FSS score >5 (n=10, 32%) were evaluated to present with fatigue symptoms, patients with borderline fatigue (n=29, 50%) had an FSS score between 4 and 5 and patients with no fatigue (n=18, 18%) had an FSS<4. When the patients were compared according to the presence of fatigue symptoms, patients with fatigue had significantly higher EDSS scores (p=0.03). BDI evaluation revealed that 33 (57%) patients had a score > or =11. MS patients with fatigue showed significantly higher BDI scores when compared to patients without fatigue (p=0.0002). A significant relationship among fatigue, disease disability and depression was observed in our study, implying the complex interplay of fatigue and depression with disability.