<jats:title>Abstract</jats:title> <jats:p>Seasonal influenza epidemics affect 5–15% of the world population with an estimated 290,000–650,000 annual respiratory deaths due to influenza. The Center for Disease Control recommends annual influenza vaccination for healthcare workers (HCWs) because not only does their occupation increase their risk of contracting influenza, but HCWs care for people at higher risk for developing influenza-related complications. Studies have shown immune responses, such as seroconversion, differ between male and female vaccine recipients, but few have focused on HCWs and their influenza vaccine responses by sex. To understand sex differences in immune responses to the influenza vaccine in the HCW population, 50 male and 50 female were recruited during the 2019–2020 influenza season as part of the Johns Hopkins Center for Excellence in Influenza Research and Surveillance (JH-CEIRS) annual serological surveys among Johns Hopkins Hospital HCWs that takes part in the annual hospital-wide vaccination campaigns. Participants were recruited just prior to receiving their annual quadrivalent influenza vaccine (QIV), which targets influenza strains A/Brisbane/H1N1, A/Kansas/H3N2, B/Colorado (Victoria lineage), and B/Phuket (Yamagata lineage). Whole blood was collected at 0, 7 and 28 days post-vaccination. Neutralizing antibody assays will be used to measure pre and post antibody titers against the H1N1 and H3N2 vaccine components. We will also analyze vaccine-specific B cell responses from peripheral blood mononuclear cells (PBMCs) at 7 and 28 days post-vaccination via flow-cytometry. This study will provide extensive data on the effects of patient sex on influenza vaccine-induced antibody responses and B cell phenotypes in the HCW.</jats:p>