In this project we performed a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via label-free shotgun proteomics. We enrolled adult (≥18 years old) patients with sepsis from community-acquired infections, diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria. Blood samples were obtained within the first 72 hours from the diagnosis of sepsis (sepsis phase) and on de day before ICU discharge (recovery phase). The Control group consisted of age matched healthy volunteers. We excluded subjects with AIDS, advanced cancer, hematological diseases, and pregnancy.