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Background: Common Variable Immunodeficiency (CVID) is classified as a 'Predominantly Antibody Deficiency' (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with cytomegalovirus (CMV) infection, a hallmark of 'combined immunodeficiency'. CMV infection also has the potential to drive immune dysregulation contributing to significant morbidity and mortality in CVID. We aim to determine the extent of cellular immune dysfunction in CVID patients, and whether this correlates with CMV infection status., Methods: We conducted a single-center retrospective cohort study of individuals with CVID at the Royal Melbourne Hospital, and identified patients with and without CMV disease or viraemia. We then isolated T-cells from patient and healthy donor blood samples and examined T-cell proliferation and function., Results: Six patients (7.6%, 6/79) had either CMV disease (pneumonitis or gastrointestinal disease), or symptomatic CMV viraemia. A high mortality rate in the cohort of patients with CVID and CMV disease was observed, with 4 deaths in the period of analysis (66.6%, 4/6). Individuals with CMV infection showed reduced T-cell division in response to T-cell receptor (TCR) stimulation when compared with CMV-negative patients., Discussion: This study demonstrates the morbidity and mortality associated with CMV in CVID, and highlights the need for focused interventions for patients with CVID at risk of CMV disease., Competing Interests: SC reports grants, personal fees and nonfinancial support from CSL and nonfinancial support from Sanofi outside the submitted work. She has undertaken contracted research on behalf of: Grifols, CSL, BioCryst & Equilium. JS has received research funding from Gilead Sciences and the NHMRC. MY has received honoraria from MSD. In the past 5 years, JD has received honoraria for educational presentations from Astra-Zeneca, GSK, Novartis & CSL. She has served on advisory boards for Sanofi-Aventis, Novartis, GSK, Astra-Zeneca, Immunosis and CSL. She has undertaken contracted or investigator initiated research on behalf of: GSK, Novartis, Immunosis, AstraZeneca, Sanofi-Aventis, Grifols, CSL, BioCryst & Equilium. She has a personal superannuation shareholding in CSL and received book royalties from ‘Fast Facts: Asthma’. CS has served as a medical advisor to Grifols, Takeda and CSL and has undertaken contracted or investigator initiated research on behalf of: Takeda, Grifols, CSL & Immunosis. VB has undertaken investigator initiated research on behalf of Immunosis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Godsell, Horton, Farchione, Howson, Margetts, Jin, Chatelier, Yong, Sasadeusz, Douglass, Slade and Bryant.)