There is FTY720 Increased ROS generation during experimental and clinical sepsis. Plasma samples from patients with septic shock that were co-cultured with human umbilical vein endothelial cells induced ROS generation, an effect related to the severity of septic shock. We and others have reported increased ROS generation by neutrophils from septic patients. Increased inducible nitric oxide synthase expression and NO metabolites have also been observed during sepsis. We found that monocytes and neutrophils from septic patients present increased NO production. In addition to their direct effects, NO and superoxide spontaneously react to form the toxic peroxynitrite anion, which leads to cytotoxic and proinflammatory responses. Elevated levels of circulating nitrotyrosine have been observed in patients with primary septic shock, and concentrations are higher in non-surviving patients compared to survivors. ROS, NO and ONOO2 have a toxic impact on mitochondria by inducing ETC dysfunction and apoptosis. The observed decreased expression of genes belonging to ETC I–V in nonsurvivors, which could reflect compromised mitochondrial respiratory function, fits well with the known deleterious effects of the oxygen and nitrogen reactive species in sepsis. Dysfunctions in zinc homeostasis have also been implicated in oxidative stress, and zinc reduces ROS via several mechanisms. Two zinc transporter families have been characterized: the zinc transporter /solute carrier 30a family and the Zrt/Irt-like protein /solute carrier 39a family. Zinc concentration in plasma has been correlated with the expression of zinc transporter genes as well as with patient outcome following sepsis. Although we do not present data on zinc concentration, we did identify three members of the SLC39A family that are down-regulated in non-survivors compared to survivors at D0. This is coupled with broad dysregulation of several genes involved in oxidative phosphorylation. Neutrophils and monocytes are the primary cells of innate immunity in host defense against infecting microorganisms. They share a number of cell functions including phagocytosis and intracellular killing of pathogens, production of cytokines and generation of reactive oxygen species. Considering, however, the specificities of each cell type, it would be interesting to evaluate if the gene expression modulation observed in mononuclear cells in our study has the same profile in neutrophils. In a previous work evaluating the TLR signaling pathway in patients in different stages of sepsis we found differences between PBMC and neutrophils gene expression, with a trend of neutrophils to present a broader up-regulation. Patient’s samples were collected 7 days after admission allowing us to analyze gene expression profile following sepsis progression and therapeutic interventions. PCA revealed that the patterns observed at admission persisted on follow-up samples in survivors and non-survivors at the onset of the syndrome is critical for patient outcome.