The role of tetraspanins is undefined, despite their detection in diverse cell types and functions. This study addresses the characterization of tetraspanin expression levels in normal peripheral blood leukocytes (PBL) and in patients with bacterial infection. Membranal and cytoplasmic expression of CD9, CD53, CD63, CD81, CD82 and CD151 in polymorphonuclears (PMN), monocytes, B and T lymphocytes was assessed using flow cytometry. Results suggested that for normal PBL, PMN are distinguished by dominant cytoplasmic CD63; monocytes and B cells prevailingly express CD53; CD82 is primarily expressed on T-cell membranes. However, a major trend of downregulation was demonstrated for the examined tetraspanins, except CD63, in all patients' PBL subtypes. Therefore, tetraspanin modulation in infections may be attributed to elevated leukocyte motility in immune reactions and this is compatible with the previous publications of tetraspanins as metastasis suppressors. This work represents the first comprehensive baseline of tetraspanin expression in normal PBL and in infectious disorders.