Introduction: Neutrophils (PMNs) are the most abundant leukocytes in the human body. They play an integral role in inflammation and combating infection, especially in the postoperative setting. PMNs are able to conduct these functions through a number of biological processes as well as release of biochemical mediators. Prostaglandin E2 (PGE2) and B-endorphin are among these mediators that play a role in the propagation and modulation of pain. With the ongoing opioid epidemic and its devastating effects on society, there has been an impetus to move away from prescribing opioid analgesics in favor of nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit Cyclooxygenase 2 (COX-2) thereby reduce PGE2 production. However there still persists a cohort of patients who do not achieve adequate analgesia with the current NSAID regiment leading to supplementation with an opioid rescue. The exact mechanisms underlying this are still not clear. The aim is to better characterize PGE2 production in human derived PMNs and determine differences between male and female samples. Materials and Methods: Healthy adults undergoing surgical extraction of partial or full bony impacted mandibular third molars, will have their blood drawn at different intervals; baseline before surgery, T0 (administration of first dose of 400 mg ibuprofen by mouth), T4 (four hours after administration), 24 hours post surgery, 7 days after surgery. PMNs will be extracted and purified via negative selection with immunomagnetic bead separation. After cell counting, cells will be divided into experimental and control arms. PMNs will be incubated with A23187 for 15 minutes and 60 minutes, and LPS for 24 hours, each with corresponding control. PGE2 levels will be measured using Cayman Chemical ELISA kit (Ann Arbor, MI). Concentrations will then be standardized before statistical analysis. Results: Analysis included 23 study participants which comprised 16 females and 7 males. Of the 23 patients, 6 (1 male and 5 females) used opioid rescue medication in addition to ibuprofen in the first week after extraction. No significant differences were observed between men and women in PGE2 production by neutrophils over time. PGE2 production was numerically higher in female-derived neutrophils at most time points, but these results were highly variable and did not attain statistical significance. The comparison of PGE2 production between partial and complete responders were also analyzed. Partial responders had significantly lower PGE2 production at T=4 compared to complete responders following stimulation with A23187 for 1 hours (p=0.038) Conclusion: Our results show that there are no sex differences in PGE2 production by human neutrophils following third molar extraction. In contrast, there was a trend toward lower PGE2 production in partial responders to ibuprofen, particularly at T=4. Among the partial responders to ibuprofen the majority were women (5 of the 6); however, a bigger sample is needed for statistical analysis and definitive conclusions.