The global prevalence of obesity is increasing and recognized as a potential risk factor for viral infections including Coronavirus Disease-19. Morbidity and mortality due to COVID-19 are higher in obesity which is considered a constant state of low-grade inflammatory milieu. Emerging data revealed a fatal connection of obesity with COVID-19 however the underlying mechanism is unclear. Leptin, a non-glycosylated peptide hormone derived from white adipose tissue that assists in metabolism, homeostasis, neuroendocrine, and other physiological functions. Additionally, leptin, as an adipocytokine has pro-inflammatory properties and acts as a connecting link between obesity and host immune responses thus, proliferates the secretion of C-reactive protein (CRP), IFN-γ, TNF-α IL-6, IL-4 and IL-2. This paper aims to address the paramount role of leptin as a potential mediator of inflammation that could exaggerate and worsen the prognosis of COVID-19 in obese individuals. Furthermore, the disproportionate efficacy of the COVID-19 vaccine in obese individuals is also highlighted.