Systemic lupus erythematosus (SLE) is acommon complex disease characterized by chronic generalized inflammation which may involve several tissues and organs. The aim of this work was to study the expression of Toll-like receptors (TLR)3 and9 in SLE patients, and to investigate their relationship to clinical features, disease activity, and damage. The current study included 24Egyptian female SLE patients and 15matched controls. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and damage using the Systemic Lupus International Collaborating Clinics (SLICC) index. Expression of TLR3 and TLR9 in B- (CD19-positive) and T-lymphocytes (CD3-positive) was studied using flow cytometry. Patient age ranged between 17and 42years (mean 26.17 ± 5.78years). There was asignificant difference between patients and controls regarding TLR3/CD3, TLR3/CD19, TLR9/CD3, and TLR9/CD19 expression (p <0.0001). There were significant correlations of TLR3/CD3, TLR3/CD19, and TLR9/CD19 with serum creatinine (r = 0.52, p = 0.009; r = 0.504, p = 0.012; and r = 0.58, p = 0.003; respectively) and negative correlations with ALT levels (r = -0.42, p = 0.04; r = -0.49, p = 0.016; and r = -0.472, p = 0.02; respectively). The results of the study suggest that TLR3 and TLR9 play arole in the pathogenesis of SLE, and have an impact on organ involvement in this disease. More studies concerning the biology and function of TLRs are required in larger patient cohorts, and may lead to development of anew class of drugs.