Highlight: ABSTRACT Coronavirus disease 2019 (COVID-19), despite being a respiratory infection, also causes neurological manifestations such as stroke due to thrombosis formation. Prior investigations have examined the correlation between COVID-19 and ischemic stroke, as well as COVID-19 and obesity. However, the mechanism of thrombosis in obese COVID-19 patients remains elusive. This review aims to examine the mechanism of thrombosis in COVID-19 patients with ischemic stroke and obesity. Chronic inflammation and impaired fibrinolysis are two major pathways responsible for thrombosis in people with obesity. Chronic inflammation activates prothrombic signaling pathways in vascular cells, resulting in procoagulant factors and adhesion molecules upregulation, anticoagulant proteins downregulation, platelet activation enhancement, and increased thrombin generation. SARS-CoV-2 enters human cells utilizing the angiotensin-converting enzyme 2 (ACE-2) receptors, which results in inflammation, which has been suggested as one of the factors contributing to thrombotic complications in COVID-19 patients. The infection also causes cytokine storm that induces atherosclerosis, plaque rupture, and superimposed thrombosis leading to brain damage. Together with endothelial injury, the cytokine storm might increase the expression of tissue factors and further promote a prothrombic state. In conclusion, the mechanisms of thrombosis in COVID-19 patients are related to direct infection of SARS-CoV-2 into the ACE-2 receptor and the cytokine storm that results in chronic inflammation and thrombosis formation. Obesity will further boost the inflammation process that leads to the formation of thrombosis and increase the risk of ischemic stroke among individuals with COVID-19 with obesity.