Background: Nephritis is a challenging domain of systemic lupus erythematosus (SLE). There is a growing need for identification of a non-invasive marker for diagnosing and monitoring nephritis. Objective: To explore the relevance of using anti-ficolin-2 antibody (Anti-FCN2) as a biomarker for detecting lupus nephritis (LN), and its relation to renal biopsy histopathology and disease activity. Patients and Methods: Sixty SLE patients were compared to 30 apparently healthy individuals. Thirty of the patients were LN patients (documented by a recent renal biopsy). Full history, examination and laboratory investigations were done. Activity was assessed by SLE disease activity index (SLEDAI) score, and Anti-FCN2 titer was measured by enzyme-linked immunosorbent assay technique (ELISA). Results: Forty-four of our SLE patients were in disease activity by SLEDAI score. Anti-FCN2 titer was significantly higher among SLE patients compared to control group (p value <0.001). It was also higher among patients with high disease activity compared to those with low disease activity and cutoff value was at 37 ng/ml (p value is <0.001). Anti-FCN2 titer was significantly higher among patients with LN compared to those without LN (p value is <0.001) with best cutoff value at 72.50 ng/ml. Regarding LN patients, it was significantly higher among patients with proliferative changes than LN patients with non-proliferative changes (p value is 0.05) with best cutoff value at 155 ng/ml. Conclusion: Anti-FCN2 shows promising results as a biomarker for lupus disease activity, especially regarding LN and proliferative changes. Further longitudinal studies on larger samples are needed to confirm.