Fatigue is among the most common and disabling symptoms in multiple sclerosis (MS). However, the relationship of perfectionism to fatigue in MS patients remains poorly understood. One hundred and twenty MS patients (79 women, 41 men) were compared with 120 healthy individuals (79 women, 41 men) to explore whether differences exist between the two groups with respect to perfectionistic characteristics and to investigate whether dimensions of positive and negative perfectionism are related to the symptomatology of fatigue. All participants were asked to complete the positive and negative perfectionism scale (PANPS), the modified fatigue impact scale (MFIS), the fatigue severity scale (FSS) and the Beck depression inventory (BDI). The results revealed that the MS group reported lower levels of positive perfectionism and higher levels of negative perfectionism as well as depressive symptoms than the control group. Perfectionism was also significantly related to fatigue symptoms in both groups. These findings suggest that the fatigue symptoms are strongly associated with perfectionistic characteristics. The negative (maladaptive) dimension of perfectionism may play a predisposing role in the development and/or perpetuation of fatigue in MS patients. The findings are discussed within the scope of current literature and implications for clinical applications are suggested.