Fatigue, as one of the most frequent symptoms in patients with multiple sclerosis (MS), has various adverse effects on the physical and mental health-related quality of life (PCS, MCS) of patients. The aim of this study was to explore whether coping mediates the relationship between fatigue and PCS and MCS. We collected data from 154 consecutive MS patients (76.0% women; mean age 40.0 +/- 9.9). Patients completed the Short-Form Health Survey (SF-36), the multidimensional fatigue inventory (MFI-20) and the coping self-efficacy scale. The mediating effect of coping was analysed using linear regressions and the Sobel z-test. In PCS significant mediation was found in some of the fatigue dimensions (general, physical and reduced Motivation), while in MCS, it was significant in all dimensions. These results can be implemented into educational programmes for patients, their caregivers or physicians, and can also be helpful in the treatment process.