<p>Serum sialic acid binding immunoglobulin-like lectin-1 (sSIGLEC-1) is a type I interferon-associated biomarker previously linked to lupus nephritis (LN) in European ancestry populations, but its utility in non-European cohorts remains poorly defined. This study aimed to validate the association of sSIGLEC-1 with LN in Egyptian SLE patients (non-European ancestry) and to test its correlation with world health organization (WHO) pathological classes, chronic kidney disease (CKD) stages, systemic lupus international collaborating clinics-renal activity score (SLICC-RAS), systemic lupus erythematosus disease activity index (SLEDAI), 24-hour urinary protein and proinflammatory cytokines. This cross-sectional study included 80 SLE patients (47 with LN, 33 without LN) and 20 healthy controls. Renal biopsy was classified according to WHO criteria. Estimated glomerular filtration rate (eGFR) and CKD stages were calculated. Median levels of sSIGLEC-1 were significantly higher in SLE patients than controls (113.5 vs. 11.2 pg/mL) and in LN patients than non-LN patients (117.7 vs. 110.0 pg/mL). Multivariable logistic regression confirmed sSIGLEC-1 as an independent predictor of LN (OR = 1.02, <i>p</i> = 0.04). sSIGLEC-1 correlated positively with SLEDAI (<i>r</i> = 0.26), SLICC-RAS (<i>r</i> = 0.31), and proinflammatory cytokines (IL-1β, IL-6, TNF-α), but did not correlate with 24-hour urinary protein (<i>r</i> = − 0.175). However, no significant differences in sSIGLEC-1 were observed across WHO pathological classes or CKD stages. ROC analysis showed poor discriminative ability for LN (AUC = 0.6928, sensitivity 93.6%, specificity 39.4%). In Egyptian SLE patients, sSIGLEC-1 is elevated in LN and correlates with disease activity but does not reflect histological severity or chronic kidney damage. Its low specificity limits diagnostic utility; however, high sensitivity suggests potential as a rule-out screening test for LN in non-European populations.</p>