Background: The pathogenesis of pediatric systemic lupus erythematosus (pSLE) is multifactorial and includes genetic predisposition and modifiable environmental factors. Lysine Acetyl transferase 2B (KAT2B), is one of the histone acetylases that regulate the gene transcription. It was linked to autoimmune diseases with variable expression in relation to various disease parameters. We sought to investigate the KAT2B expression on peripheral blood mononuclear cells (MNCs) in patients with pSLE and its relation to biomarkers of lupus flare, major organ involvement, SLE disease activity index (SLEDAI), and therapeutic modalities used. Methods: This crosssectional comparative study comprised 30 patients with SLE who fulfilled at least four of the System Lupus International Collaborating Clinics (SLICC) classification criteria. Thirty age- and sex-matched healthy children were included as a control group. The patients were subjected to clinical evaluation including the SLEDAI, and lupus flare laboratory markers. KAT2B expression on MNCs was measured by ELISA in the pSLE patients as well as the control group. Results: KAT2B expression on the MNCs was significantly lower among the pSLE patients than the healthy controls (p <0.001). Patients with moderate and severe lupus activity had significantly lower KAT2B expression on MNCs than those with mild activity as judged by the SLEDAI (p=0.03). The KAT2B expression was not significantly correlated to the studied biomarkers of lupus activity (ESR, anti-DNA or C3) but was negatively correlated to the extent of renal affection in terms of the 24 hours urinary protein level (p=0.024). The findings are limited by the sample size. Conclusion: From this pilot study, the low expression of KAT2B on MNCs seems to be linked to pediatric SLE disease activity. Wider scale and prospectively designed studies are needed to validate this observation and to explore the effect of disease remission on KAT2B expression in pSLE activity.