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Objectives The primary aim of this study was to investigate the association between disease activity and fatigue severity in patients with SLE. The secondary aim was to analyze the impact of age, disease duration, and corticosteroid (CS) therapy on fatigue severity.Methods This cross-sectional study included 49 patients fulfilling the 2019 ACR/EULAR classification criteria for SLE. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) questionnaire, with scores ranging from 0 to 52, where lower scores indicate greater fatigue. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS). Based on SLE-DAS, patients were classified as: remission (SLE-DAS = 0), low (SLE-DAS<= 2.08), moderate (2.08 < SLE-DAS <=7.64), or high disease activity (SLE-DAS > 7.64). Patients were grouped by current prednisone dose into three categories: <=5 mg, >5–<=10 mg, and >10 mg.Results The cohort consisted predominantly of women (96%), with a mean age of 53.1 ± 14.7 years and mean disease duration of 15.4 ± 11.4 years. Median scores were: FACIT-F 30 (IQR 17–42), SLEDAI-2K 4 (2–7), and SLE-DAS 4.48 (1.32–9.25). Fatigue severity showed no significant correlation with disease activity assessed by either index (p > 0.05). Fatigue correlated negatively with age (r = –0.59, p < 0.05) and was unrelated to disease duration (p > 0.05). Median FACIT-F scores across SLE-DAS categories were 41.5 (remission), 36 (low), 35 (moderate), and 26.5 (high disease activity), with no significant differences between groups (p > 0.05). Patients receiving CS therapy (n = 41), reported significantly higher fatigue than those not on CS (n = 8, p < 0.05). Among patients receiving CS, median FACIT-F scores across prednisone dose groups (<=5 mg, >5–<=10 mg, >10 mg) were 18, 30, and 30, respectively, with no significant differences (p > 0.05).Conclusions Our study found no association between disease activity and fatigue in patients with SLE. CS therapy was associated with greater fatigue, regardless of dose, and older patients exhibited greater fatigue. Disease duration showed no significant impact on fatigue severity.