COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.