Background: Coronavirus disease 2019 (COVID-19) is a new infectious disease caused by the SARS-CoV-2 coronavirus, which first appeared in Wuhan and quickly spread around the world. The Middle-East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) outbreaks in 2003 and more recently have demonstrated how lethal CoVs can be when they infect humans across the species barrier. The novel severe acute respiratory syndrome coronavirus 2 has threatened the world in many ways (SARS-CoV-2). Zonulin is a member of a protein family whose first member, pre-haptoglobin 2 (HP2), was discovered nearly ten years ago. (Rittirsch D 2013).Materials and Methods: A total of 120 Covid-19 patients' serum samples were collected and an apparently healthy group (n=60) with an age range (of 35-75) years, was admitted from AL- Amal Hospital. Zonulin levels were measured by enzyme-linked immunosorbent assay (ELISA) (kit. Metabolic parameters were measured by enzymatic spectrophotometer methods. The correlation coefficients between serum Zonulin levels and age, BMI, Elements and electrolytes were also evaluated.Results: Serum Zonulin, CRP, D-dimer and ferritin levels were significantly higher in Patients with COVID-19 (324.4±12.46) vs in control (79.69±11.77), (42.67±1.84) vs in control (3.36±0.25), (4188.21±198.73) vs in control (289.43±251) and (738±20.09) vs in control (130.66±9.2) (P <0.001). The correlation of Zonulin levels in COVID-19 patients was significantly positive with age, CRP, D-dimer and ferritin levels but negative with Iron, Ca and Na levels. The serum of Zonulin levels in moderate COVID-19 patients significantly high compared with the critical and severe patients group.Conclusions: Serum Zonulin levels increased in COVID-19 patients, especially in severe cases. Therefore, Zonulin levels demonstrate a prognostic value for predicting the severity of COVID-19. Continuous Zonulin results throughout the study period revealed that the severe group's values were higher than those of the non-severe group.