Retrospective studies demonstrate that during the 2009 H1N1 pandemic, obesity was identified as a risk factor for hospitalization, mechanical ventilation, and mortality upon infection. This study is a review which focuses on how obesity and cardiovascular disease impact influenza response. A higher body mass index and metabolic syndrome in patients with influenza have shown an increased risk and length of hospitalization, increased disease severity, morbidity, and mortality during lower respiratory tract infections. Obesity causes a chronic state of inflammation in a generalized and constant way with negative effects on immunity. In fact, obese people have delayed immune responses to influenza virus infection and experience slower recovery from the disease. Thus, recent recommendation advocates the priority of vaccination against influenza in obese patients. Furthermore, cardiovascular diseases, such as ischemic heart disease and heart failure combined with influenza A infection, can trigger acute heart failure exacerbations that increase the overall mortality in a hospitalized setting. The cardioprotective mechanism of influenza vaccination may not function effectively in obese cohorts, thus authors conclude that in order to prevent these complications and in the absence of special consideration treatments for this population, a weight-loss approach is highly recommended.