Sepsis is characterized by life-threatening organ dysfunction caused by dysregulated host response to infection. An underlying cause of sepsis is dysregulation of neutrophil-endothelial interactions. To date, therapeutic approaches are supportive, and there are no effective drugs that target immune dysregulation and alter neutrophil-endothelium function. In our prior investigation, three distinct neutrophil functional phenotypes (i.e., Hyperimmune, Hypoimmune and Hybrid) were identified in sepsis patients through a comprehensive analysis encompassing clinical, organ-on-chip and proteomic assessments. In this study, we utilized bioinformatics to elucidate cellular processes impacting each neutrophil phenotype. These findings were leveraged to identify potential FDA-approved therapeutics that could be repurposed to target proteins within each phenotype highlighting the impact in normalizing altered neutrophil-related responses such as adhesion and migration. A protein-protein interaction network was employed to prioritize these target proteins. Finally, we identify several FDA approved therapeutics for treating sepsis including a (pre)clinical trial therapeutic targeting VTN in the Hybrid phenotype, a therapeutic targeting TRPV2 in the Hypoimmune phenotype and a (pre)clinical trial therapeutic targeting H2AC21 in the Hyperimmune phenotype. Thus, we not only identified critical cellular processes impacting each neutrophil phenotype but also reveal those protein targets that could be prioritized for future validation in the treatment of sepsis.