Abstract Background The novel coronavirus, SARS-CoV-2, has caused a global outbreak starting December 2019 in China. Since then, it caused a global pandemic infecting more than 140 million patients worldwide. The viral transmission happens primarily through direct contact or droplet transmission. However airborne transmission in certain circumstances was demonstrated in multiple studies. Aim of the Work Primary Objective: Comparing Protein C & S levels in normal population to patients infected with COVID 19. Secondary Objective: Measuring the correlation of protein C & S levels in plasma & it’s relation to COVID 19 infection severity. Patients and Methods This is a case control study measuring Protein C & S levels in patients infected with COVID 19 compared to normal population over a period of six months, to assess their consumption as an anti-thrombotic protein against COVID 19 infection associated state of hypercoagulability. The study included a hundred participant divided into two groups. The first group had sixty patients infected with COVID 19 and the second group had forty normal healthy Egyptian adults. Results Our study showed that when comparing the patients blood indices to the controls there was a significant increase in TLC. Regarding the serum chemistry, our study showed that in the patients group the serum creatinine and blood urea nitrogen. For liver enzymes and liver function tests, our study showed that AST, ALT, Alkaline phosphatase, and gamma G. T. all of them are elevated in the Covid 19 patients when compared to the control group. Conclusion This study concluded that the level of protein C activity and the level of Protein S activity are both decreased in patients of the Covid 19 when compared to normal population. It also, concluded that the decrease in their levels is in statistical significance relation to the disease severity in the Covid 19 patients. Also, their levels were lower in patients who developed DVT or thrombosis in the Covid 19 infected group. Finally in chronic kidney disease patients only protein C was related to the disease severity not protein S nor D-dimer.