COVID-19 or coronavirus disease 2019 which first appeared in China, become a global health issue. Ghrelin is a peptide hormone that increases food intake and decreases fat utilization, resulting in weight gain. Ghrelin influences nutritional intake and the release of growth hormone, and therefore development and growth. IL-6 is the common pro-inflammatory cytokines. The aim of this study is to evaluate the levels of Ghrelin and IL-6 in obese patients infected with COVID-19 as early predictor markers of COVID-19 severity. In this case-control study ,60 obese subjects, included 30 obese volunteers without any chronic disease or COVID-19 and 30 obese patients infected with COVID-19 and admitted to Al-Sader Medical City and Al-Amal hospital in Najaf, Iraq, divided into three cases according to the severity (13 mild/moderate), (10 severe) and (7 dead) with the age ranged between (25-60) years. Thirty (20 male and 10 female) apparently healthy subjects were selected as control group, their age and sex were comparable to the patients. The enzyme linked immunosorbent assay (ELISA) kits used to measure serum Ghrelin and IL-6 levels. The serum level of Ghrelin was significantly decreased, while serum level of IL-6 increased in non-survived and sever cases than the mild/moderate cases. Ghrelin negatively correlated with serum level of IL-6 in obese patients infected with COVID-19. IL-6 and Ghrelin levels in the obese patients can be a useful prognostic tool associated with COVID-19 to predicts the SARS-COV-2 severity in the obese patients with COVID-19.