Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder associated with various comorbid conditions. Here, we assessed the burden of comorbidity in patients with SLE in Egypt using the Charlson Comorbidity Index (CCI) and determined its association with the disease characteristics. Patients and Methods: In this retrospective study, data of patients with SLE in Egypt were collected from the medical records. This included demographic data, clinical characteristics, comorbidities, and baseline SLE disease activity index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores at the last visit. The CCI score was calculated for each patient. The data of deceased patients were also collected. Results: Overall, 152 patients were included in this study. The most common comorbidities excluded from the CCI were serious infections (27%) and hypertension (23%); the most common comorbidities included in the CCI, apart from the connective tissue disease, were moderate or severe renal disease (12.5%), peptic ulcer (9.9%), and diabetes mellitus (9.9%) without end‑organ damage. The mean CCI score was 1.9 and was significantly correlated with the disease duration, SLEDAI, and SDI. The death rate was 7.9%; the most common cause of death was infection (50%). Death was significantly associated with a high score of SLEDAI, SDI, and CCI. The mortality rate was higher in patients with SLE along with hypertension, renal affection, hyperlipidemia, infection, and tumors (P < 0.05). Conclusion: Patients with SLE in Egypt experienced comorbidities and high CCI scores that affected their survival.