Abstract Introduction: Renal involvement is one of the main determinants of poor prognosis of systemic lupus erythematosus (SLE). Kidney biopsy is an invasive procedure and accompanied by potential risks. Thus defining a reliable biomarker of kidney involvement in SLE is highly desirable. Aim of the work: To assess the role of anti-C1q Ab in combination with anti-dsDNA Ab in detection of SLE disease activity and renal involvement (lupus nephritis). Patients and methods: Anti-C1q Ab and anti-dsDNA antibodies were determined in 60 randomly selected adult SLE patients one of them refused the biopsy and those who completed the study were 59. The control group included 25 age and sex matched volunteers. According to lupus nephritis (LN) and SLEDAI score, patients were divided into four groups: group 1, 11 patients had active disease with LN; group 2, 20 patients had inactive disease with LN; Group3, six patients had active disease without LN; group 4, 22 patients had inactive disease without LN. Results: A significant association of active lupus nephritis detection and the presence of either one or both of the studied antibodies (anti-C1q Ab or anti-dsDNA). None of the patients of group 1 had anti-C1q Ab only, and none was negative for anti-C1q Ab and anti-dsDNA Ab together. Levels of anti-C1q Ab and anti-dsDNA Ab were significantly higher in more active LN than less active LN. Anti-dsDNA and anti-C1q antibodies sensitivity and specificity for detection of more active LN was 85.0% and 64.0% and 70.0% and 55.0%, respectively, and 75.0% and 91.0% for both. Both antibodies had a positive correlation with SLEDAI score and proteinuria and a negative correlation with C3 reduction. A high significant positive correlation was detected between anti-C1q Ab and anti-dsDNA Ab. Conclusion: Anti-C1q Ab, in combination with anti-dsDNA Ab may serve as potential reliable and none invasive markers of SLE disease activity and renal involvement to avoid unnecessary renal biopsies.