Sepsis is one of the highest causes of mortality in hospitalized people and a common complication in both surgical and clinical patients admitted to hospital for non-infectious reasons. Sepsis is especially common in older people and its incidence is likely to increase substantially as a population ages. Despite its increased prevalence and mortality in older people, immune responses in the elderly during septic shock appear similar to that in younger patients. The purpose of this study was to conduct a genome-wide gene expression analysis of circulating neutrophils from old and young septic patients to better understand how aged individuals respond to severe infectious insult. We detected several genes whose expression could be used to differentiate immune responses of the elderly from those of young people, including genes related to oxidative phosphorylation, mitochondrial dysfunction and TGF-β signaling, among others. Our results identify major molecular pathways that are particularly affected in the elderly during sepsis, which might have a pivotal role in worsening clinical outcomes compared with young people with sepsis.