Background: Fat mass and obesity gene (FTO) polymorphism had linked with risks and health problems related to obesity in many studies and different population. Our study was designed to investigate association of FTO rs9939609 with COVID-19 severity and biochemical parameters such as serum triacylglycerol, cholesterol, transaminases and plasma glucose in obese Egyptian population. Methods: TaqMan SNP Genotyping Assay of FTO gene rs9939609 (A < T) in a sum of 253 obese cases infected with COVID-19. Fasting samples of serum insulin, plasma glucose, lipid profile, as well as ALT and AST were measured. Evaluation of the association between COVID-19 severity and genotype distribution was done via logistic regression tests and Chi-square. Results: The association of COVID-19 severity with genotype distribution was significant (χ2 = 8.6/P = 0.014) and odds ratio under dominant model (OR = 1.86, P = 0.029 and 95%C.I = 1.08-3.4) and recessive model (OR = 2.95,P = 0.017 and 95%C.I = 1.23-6.42) was increased. HDL-C levels in (AA) subjects (P = 0.009) were significantly lower in comparison to (TT). Moreover, ALT levels in (AA) genotype subjects (P = 0.02) were significantly higher and persisted in accordance with correction of major confusing parameters as TAG and BMI, while aborted with conservative Bonferroni adjustment. Conclusions: The current study displayed that Fat mass and obesity gene (FTO) rs9939609 is a risk factor for COVID-19 severity in obese individuals that may aid to understand the pathophysiology of the disease progression and highlighted that lipid metabolism may play a role in this association.