Introduction: Patients with systemic lupus erythematosus (SLE) experience significant fatigue, a debilitating symptom associated with reduced quality of life. There has not yet been agreed on a simple and reliable method for assessing fatigue in SLE. Objectives: To investigate the internal consistency, test–retest reliability and construct validity (convergent and discriminant validity) of the Modified Fatigue Impact Scale (MFIS) in patients with SLE. The secondary objective was to investigate the contribution of disease activity and organ damage to fatigue. Methods: Fatigue was assessed using the MFIS in 61 patients with SLE. Internal consistency of MFIS was assessed with Cronbach’s alpha (α) and Principal Component Analysis. Test–retest reliability was evaluated using the intraclass correlation coefficient (ICC). Construct validity was studied using Spearman’s rank correlation (r s). Associations between MFIS and disease activity and organ damage were estimated with r s. Results: Internal consistency of the MFIS was excellent with Cronbach’s α = 0.97 (95% confidence interval (CI): 0.96–0.98) for the complete scale. Test–retest reliability was good with ICC = 0.89 (95% CI: 0.78–0.95, p < 0.001). Construct validity was confirmed by Spearman’s correlation (VT-SF36: r s = −0.73, p < 0.001. MH-SF36: r s = 0.70, p < 0.001). No significant correlation was found between the MFIS and SLEDAI (r s = 0.03, p = 0.83). There was a moderate correlation between MFIS and SLICC Damage Index (r s = 0.43, p < 0.001). Conclusion: The present study found the MFIS to be a reliable and valid instrument for assessing fatigue in SLE. Further investigations are needed to clarify if an association between measured fatigue and disease components exists.