Dexamethasone is approved as second-line therapy in pediatric chronic immune thrombocytopenic purpura (ITP). Several B-cell abnormalities have been described in ITP pathogenesis. This study assessed the effects of high-dose dexamethasone (HD-DXM) on the percentages and absolute counts of CD19+ CD24hiCD38hi regulatory (Bregs) and CD19+ CD27+ memory B lymphocytes (Bmems) in children with chronic ITP during active bleeding. The study was a prospective cross-section case-control, included 20 children with chronic ITP and uncontrolled bleeding. Children received a single daily dose of HD-DXM for 4 days. Blood samples were withdrawn from patients just before HD-DXM therapy and on day 5 to evaluate the platelet counts and flow cytometric analysis of Bregs and Bmem. The patients' platelet counts significantly increased after 5 days of the initiation of therapy (P= 0.0001). Bmems percentage and absolute counts were significantly higher in patients before treatment (P= 0.0007), and decreased after HD-DXM therapy (P= 0.97) compared with the controls. Bregs percentage and absolute counts were significantly lower before treatment (P= 0.0003) and increased after HD-DXM (P= 0.003). There is a negative correlation between platelet counts and Bregs percentage and absolute count Bmems percentage before and after HD-DXM, whereas a positive correlation between platelets and Bregs before and after dexamethasone has been reported.