Background: Infective endocarditis (IE) is a severe disease with high morbidity and mortality rate. Poor immune response and autoimmunity have been reported in patients with IE and result in different complications such as severe sepsis, glomerulonephritis, arthritis, coagulopathy and embolization. This study aims to investigate the role of immune system in the pathogenesis of IE through assessment of memory and naïve T and B lymphocytes and T regulatory cells (T regs). Methods: Twenty IE patients and twenty healthy age and sex matched donors were included in the study. Flow cytometry was used to asses the naïve and memory subsets of peripheral blood lymphocytes using cell surface markers CD4, CD19, CD45RO, CD45RA, CD27 and IgD. T regs were characterized by co-expression of CD25/FoxP3 among the CD4+ T cells. Results: IE patients had significant lower number of CD45RO+CD4+ memory T cells when compared to healthy control (p=0.03). No differences were observed regarding CD45RA+CD4+ naïve T cells, CD19+CD27+ memory B cells and CD19+IgD+ naïve B cells between the IE patients and healthy control. However, IE patients had significantly lower percentage and number of T regs (p=0.039, p=0.009 respectively). Conclusion: IE patients suffer from immune system dysfunction which contribute to the disease course and complications. The decrease in the CD45RO+CD4+ memory T cells can partly explain why IE patients cannot effectively clear the infection before the invading pathogen replicate and cause tissue damage. The defect in T regs may underlie the autoimmunity and occurrence of autoantibodies reported in IE patients