Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity-driven predictors of poor COVID-19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID-19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.