Background: Systemic Lupus Erthematosis (SLE) is a chronic autoimmune disorder that affects multiple organ systems and also affects the skin and oral mucosa, with the exact cause is unknown. Many hypotheses try to explain the role of the complement C3, C4 in the pathogenesis of SLE. The aim of this study is to determine levels of serum complement C3 and C4 in patient with SLE, so that we may explain its role in diagnosis and pathogenesis of the disease. Methods: Twenty patients were informed from outcome patients of Dermatology Unit in El-Azhar University suffering from SLE. All the patients included in this study fulfilled 4 or more of the American Rheumatism Association classification Criteria for SLE. Blood samples from These 20 SLE patients (18 females and 2 males) aged from 20 to 45 years old were collected. Complement C3 and C4 were measured using radial immunodiffusion plates system technique. Clinical parameters such as Erythrocyte Sedimentation Rate (ESR), Total Protein (TPR), Serum Creatinine and Antinuclear Antibody (ANA) of those patients were considered in order to compare and explain the data obtained for the levels of C3 and C4. The data were collected and statistically analyzed. Results: Most of patients were female 90% and only 10% male. Of all patients, 60% have low level of serum C4, 40% have normal level of serum C4, 25% have abnormal level of serum C3, and 75% have normal level of serum C3.Statistical analysis of the data on the correlation between C4, and disease activity revealed significant (P> 0.05) correlation, however no significant correlation was found between C3 and disease activity. Analysis on the correlation between C3 and C4 with TPR, S. creatinne, and ESR, showed no significant correlation. No significant relationship was also found between C3 and C4.All patients have had high TPR, S. creatinne and ESR. All patients have had positive ANA which is an important marker of SLE as an auto immune disease. Conclusions: Patients showed different degrees of oral and systemic manifestations, which exacerbate and become acute with decreased level of complement C4 and instability of C3 level. Accordingly, the low level of C4 was associated with the development and exacerbation of SLE. Increased C3 levels is solely due to activity through the alternative pathway in SLE patients