SLE is a multisystem autoimmune disorder with various clinical presentations and immunological abnormalities with etiology that has not been fully understood. It is characterized by abnormalities in B lymphocytes in particular that lead to production of autoantibodies. Toll-like receptors (TLRs) are pattern recognition receptors in innate immunity that may be involved in recognition of self-antigens and production of pathogenic autoantibodies. This study was aimed to examine the proportions of B lymphocyte subsets and to determine TLR9 expression in B cell subsets in Omani SLE patients and healthy controls and to study the relationships between TLR9 expression and levels of autoantibodies and/or disease activity. To accomplish these aims, 33 SLE patients and 22 healthy controls were enrolled in the study and peripheral blood mononuclear cells (PBMCs) were obtained. PBMCs were stained for cell surface markers specific for B cell subsets and for intracellular TLR9, and stained cells were analyzed by a FACSCaliber flow cytometer. The levels of autoantibodies patient sera were analyzed by indirect immunoflourescence staining and ELISA, and the disease activity was determined by SLE disease activity index (SLEDAI). The results showed that the percentages CD197 B cells were similar between the SLE patients and controls, and the frequencies of CD19+ CD27* memory B cells and CD19* CD38+ B cells differentiating into plasma cells didn't show statistically significant difference in the patients when compared with the subsets in healthy controls. Although a trend in increased expression of TLR9 in B cells was observed in 31.2% (10/32) of the SLE patients, there was not a statistical significant difference between the patients and healthy controls. Similarly, TLRO expressions in CD19+ CD27+ and CD19* CD38+ B cell subsets were not significantly different between the two groups even though a few patients, 3/14 and 2/6 patients examined for CD19+ CD27* and CD197 CD38+ B cell subsets respectively, showed an increased TLR9 expression. Among the B cells in both groups, the expression of TLR9 was significantly higher in CD197 CD27* memory cells compared to CD19+ CD27 naive cells. In contrast, TLR9 expressions in CD197 CD38+ and CD19+ CD38 B cell subsets were comparable. Serum analysis showed that all SLE patients 33/33 (100%) were seropositive for anti-nuclear antibody (ANA) and anti-double stranded DNA (dsDNA) was detected in 26/33 (79%). Examinations of the relationships between the TLR9 expression and anti-dsDNA antibody levels or disease activity revealed no significant correlation between TLR9 expression and the antibody levels or the disease activity. However, the frequencies of TLR9 expressing B cells were significantly higher in patients with SLEDAI >5 than that in healthy controls. In conclusion, the lack of significant differences in B cell subset frequencies and TLR expression between SLE patients and healthy controls is most likely due to the relatively quiescent disease state of the patients and hydroxychloroquine, one of the therapeutic drugs used to treat these patients, that has been shown to decrease TLRI expression.