Background <p>Several patient-reported outcome measures assess fatigue and fatigability in multiple sclerosis (MS), yet their psychometric properties require evaluation for appropriate selection.</p> Objective <p>This study examined the psychometric properties of two perceived fatigue measures (Modified Fatigue Impact Scale [MFIS)], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], one perceived fatigability measure (Pittsburgh Fatigability Scale [PFS]) and one combined measure (F-2-MS).</p> Methods <p>One hundred PwMS completed questionnaires assessing perceived fatigue, fatigability, and other secondary disease characteristics of MS. Analyses included floor and ceiling effects, reliability, and validity of the self-reported fatigue and fatigability measures.</p> Results <p>No measures showed floor or ceiling effects (&lt; 20%). Internal consistency was good (α &gt; .80) for all except F-2-MS. Only MFIS demonstrated low measurement error (standard error of measurement % = 8.78 (&lt; 10%)). Convergent validity (<i>r</i> ≥ .80) was supported for MFIS with FACIT-F and F-2-MS. Discriminant validity was supported with all correlations &lt; .80. Disability group differences were significant for MFIS, FACIT-F and PFS (F (10, 184) = 5.80, <i>p</i> = &lt; .001), but not for F-2-MS.</p> Conclusion <p>Minimal floor and ceiling effects, strong reliability, and good discriminant validity across all measures support their use in clinical and research settings. MFIS is most robust for perceived fatigue, and PFS for perceived fatigability.</p>