ckground. MicroRNAs (miRNAs) contribute to the development and progression of systemic lupus erythematosus (SLE) via affecting a wide range of targeted genes and facilitating the development of lupus nephritis (LN). Aim. To analyze the serum expression of miR-181a and miR-223 in SLE patients and to assess whether they could serve as novel biomarkers for SLE diagnosis and to distinguish LN. Subject & methods. This study included 70 control subjects and 116 patients with SLE (67 non-LN and 49 LN groups). Circulating miR-181a and miR-223 expression levels were analyzed among Egyptian population using real time polymerase chain reaction. Results. Up-regulation of miR-181a was detected among SLE patients compared to healthy controls and higher values were reported among LN group compared to non-LN group. Down-regulation of miR-223 was reported among SLE patients compared to controls and lower values were reported among LN group compared to non-LN group. The higher miR-181a expression and the lower miR-223 expression were associated with higher stages of LN. SLE disease activity index (SLEDAI), proteinuria and serum creatinine were independently correlated with miR-181a and miR-223 among SLE patients by linear regression analysis. ROC curve analysis revealed that combined miR-181a and miR-223 expressions increased the sensitivity and specificity for the diagnosis of SLE and further to distinguish LN from non-LN patients. Conclusion. MiR-181a and miR-223 could play a role in evaluating SLE disease progression and prognosis. Combined miR-181a and miR-223 expression analysis could serve as novel non-invasive fingerprints in the diagnosis of SLE and predicting LN among Egyptian patients. Keywords: miR-181a; miR-223; SLE; lupus nephri