Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. To explore the overall status of EBV, TLR7, TLR9, and IFN-α gene expression in 32 patients suffering from SLE and 32 healthy controls. Plasma and PBMCs were separated from fresh whole blood. To measure EBV DNA load and mRNA levels of IFN-a, TLR-7 and9 in PBMCs, molecular techniques were employed. The production of IFN-α, ds-DNA IgG antibody, and EBNA-1 IgG levels were also measured in plasma by ELISA. SLE patients showed significantly higher EBV load (p=0.001) and transcriptional levels of TLR7 (p=0.0001), IFN-α (p=0.0001), and TLR9 (p=0.0001) than controls. Moreover, the plasma levels of IFN-α (p=0.0002) and EBNA-1specific IgG antibodies (p=0.01) were significantly higher in SLE patients. The results stressed on the potential role of EBV infection and TLRs in SLE patients although more research is needed to determine the global impact that EBV infection can have on immune signature in patients with SLE.