Sepsis is defined as the systemic inflammatory response to infection. Phospholipase A2 (PLA2) plays an important role in inflammation processes by initiating the production of inflammatory mediators. The role of cytosolic PLA (cPLA2) has not yet been identified in inflammatory and infectious disease clinical settings. The aim of the present research was to determine whether cPLA2 activity has a role during sepsis. Since neutrophil activation has been documented during sepsis, these cells were chosen as a model to evaluate the function of cPLA2 in this clinical setting. cPLA2 was studied at 3 levels: activity, protein expression, and messenger RNA (mRNA). Neutrophils from 32 septic patients with and without bacteremia were examined, cPLA2 activity was measured using labeled phosphatidyl choline vesicles as a substrate, and total PLA2 was determined by the release of labeled arachidonic acid from prelabeled cells. A significant increase in cPLA2 activity, protein expression, and total PLA2 activity in neutrophils was detected during sepsis, mRNA levels, detected by reverse transcriptase- polymerase chain reaction, were significantly higher during sepsis, indicating that the increase in the amount of cPLA2 is regulated on the mRNA level. The significant elevation of cPLA2 activity and expression in neutrophils during sepsis suggests that this enzyme plays a major role in neutrophil function in this clinical setting.