Aim: The aim of the study was to assess serum levels of MPO in lupus nephritis class III and IV patients and their relationship with disease activity parameters.Methods: Forty patients with Systemic Lupus Erythematosus (SLE) and forty healthy controls were investigated in this study diagnosed according to European league against rheumatism &American colleague of rheumatology 2019(EULAR/ ACR) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and laboratory parameters, including erythrocyte sedimentation rate, ANA, anti-ds DNA antibody, complement 3, complement 4 levels and CRP were analyzed. The serum myeloperoxidase (MPO) was determined using enzyme-linked immunosorbent assay. Results: The mean Anti ds DNA, complement 3&4, ESR, and ANA titer were significantly higher among cases than controls. The mean myeloperoxidase marker was significantly higher among cases than controls (p value <0.001*). Serum myeloperoxidase had a significant role in prediction of lupus nephritis at a cut off more than 178.5; it can predict the LN with 80% sensitivity, 50% specificity, 61.5% PPV and 71.4% NPV. The A/C ratio seemed to be highly predictor for LN than the serum myeloperoxidase as at a cut off more than 30, it can predict the LN with 100% sensitivity, 97.5% specificity, 97.6% PPV and 100% NPV. Conclusion:   This study suggests a good correlation between MPO and SLE disease activity index indicating its direct involvement in inflammatory conditions associated with disease.