['Antimicrobial resistance threatens to undermine treatment of severe infection; new therapeutic strategies are urgently needed. Preclinical work shows that augmented passive immunotherapy with P4 peptide increases phagocytic activity and shows promise as a novel therapeutic strategy. Our aim was to determine ex vivo P4 activity in a target population of patients admitted to critical care with severe infection.', 'We prospectively recruited UK critical care unit patients with severe sepsis and observed clinical course (≥3 months postdischarge). Blood samples were taken in early (≤48\u200ah postdiagnosis, n\u200a=\u200a54), latent (7 days postdiagnosis, n\u200a=\u200a39), and convalescent (3-6 months postdiagnosis, n\u200a=\u200a18) phases of disease. The primary outcome measure was killing of opsonized Streptococcus pneumoniae by neutrophils with and without P4 peptide stimulation. We also used a flow cytometric whole blood phagocytosis assay to determine phagocyte association and oxidation of intraphagosomal reporter beads.', 'P4 peptide increased neutrophil killing of opsonized pneumococci by 8.6% (confidence interval 6.35-10.76, P\u200a<\u200a0.001) in all phases of sepsis, independent of infection source and microbiological status. This represented a 54.9% increase in bacterial killing compared with unstimulated neutrophils (15.6%) in early phase samples. Similarly, P4 peptide treatment significantly increased neutrophil and monocyte intraphagosomal reporter bead association and oxidation, independent of infection source.'] Does augmented Passive Immunotherapy with P4 Peptide improve Phagocyte Activity in Severe Sepsis?