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Individuals with obesity are at increased risk of morbidity and mortality from both influenza virus infections and COVID-19. Both influenza and SARS-CoV-2, the viral agent of COVID-19, are respiratory viruses, and the immune response to the infection is similar for both viruses. Using both pre-clinical animal models and clinical research studies with influenza vaccination, we have found significant influenza-specific immune dysfunction with obesity. This immune impairment results in adults with obesity being 2X more likely to develop influenza, despite vaccination. Mechanistically, the impairment is likely related to metabolic alterations in the immune cell population, driving immune dysfunction. Preliminary data with COVID-19 suggests some of the same obesity-driven immune dysfunction against influenza virus may also be found with SARS-CoV-2 infections, suggesting that, compared with a lean population, the obese population may not receive the equivalent level of protection with COVID-19 vaccines.