ObjectivesThe study provided validity and reliability evidence of the Fatigue Severity Scale (FSS) in Greek patients with multiple sclerosis (MS).Materials and MethodsThe FSS was administered to 72 MS patients, without co morbid fatigue and 75 matched paired controls with respect to gender and age. Both groups responded to the FSS, SF-36v2, BDI-II and a demographic questionnaire on two time points separated by a 1-week interval. Exploratory and confirmatory factor analysis was performed to test construct validity, concurrent and divergent validity, internal and test-retest reliability were also examined.ResultsExploratory and confirmatory factor analysis, intercorrelations with BDI-II (r = 0.552, p < 0.01) and SF-36v2 vitality (r = −0.715, p < 0.01) and physical functioning (r = −0.673, p < 0.01) subscales, and differences between patients and non patients (t(145) = 6.007, p < 0.001), revealed sufficient construct, concurrent and divergent validity evidence. The factor analysis demonstrated a unidimensional structure Cronbach alpha (0.953) and ICC (0.889) was high, indicating that the responses of our sample were internally consistent and stable across time.ConclusionThe Greek version of FSS is valid and reliable and may be used by clinicians and researchers to assess fatigue of Greek MS patients.