Background: In systemic lupus erythematosus (SLE), the increased rate of apoptosis and inefficient clearance of apoptotic cells leads to activation of NLRP3 inflammasome. NLRP3 overstimulation is proven to be involved in the pathogenesis of lupus nephritis (LN). We sought to measure the expression of NLRP3 among pediatric patients with SLE and LN, in correlation to markers of activity. Methods: A pilot, cross-sectional controlled study was conducted from Jan 2022 to Jan 2024. Fifty-six patients with confirmed SLE and active LN with or without other system activity were compared to age and sex-matched 56 healthy controls as regards expression of NLRP3 protein using enzyme-linked immunosorbent assay (ELISA) technique (Human NLRP3 ELISA Kit). Results: Peripheral expression of NLRP3 was significantly higher among patients with juvenile SLE with active LN than controls (p-value <0.001). Other systemic activities were present within 27/56 patients, 11 patients had cardiac manifestations and 16 patients had neurological manifestations. SLE disease activity index (SLEDAI) was 32.4 (SD 7.6) and was significantly correlated to peripheral NLRP3. LN Class, level of C3 consumption, proteinuria, and kidney functions were not correlated to levels of NLRP3 protein. Conclusion: Expression of NLRP3 inflammasome in the peripheral blood was significantly elevated in juvenile SLE with LN compared to controls, with significant correlation to SLEDAI, but not to LN Class or markers of activity. Comparison between pediatric patients with SLE with and without LN and comparing renal NLRP3 inflammasome to its peripheral expression in patients with LN are recommended.