As a global burden, the coronavirus disease 2019 (COVID-19) pandemic is going on spread. It has many clinical manifestations and impacts on humans worldwide. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes systemic illness through its known receptor binding to angiotensin-converting enzyme 2 (ACE2) which is expressed in various tissue types in the human body. Its infection and systemic condition lead to physical and psychological stress for the patients. During critical illness, and ongoing inflammation, physical and psychological stress both contribute to the patient’s outcome. Pre-existing or underlying psychological conditions also affect COVID-19 patients and lead to poorer prognosis. Stress causes several imbalances including neurohormonal, pro-inflammatory, and metabolic alteration. Ongoing stress and COVID-19 both increase systemic inflammation through interleukin 6 (IL-6), hyperglycemia, and uncontrolled sympathetic drive. These conditions pile up into the vicious cycle of poor prognosis and even mortality. This review article discusses the mechanism of stress to induce inflammation and hyperglycemia that correlated with the poorer outcome in COVID-19 patients. Because of its important role in COVID-19, approaches should be made to overcome stress and homeostatic imbalance caused by stress conditions in COVID-19 patients.