Objective: The aim of this study is to find out the link between the involvement of complement activation in the inflammatory reactions in COVID-19 patients, the deterioration of the clinical status and development of sever COVID-19 in those patients. Methodology: The study included 274 COVID-19 patients, divided into three groups; group1: severe COVID-19 patients (n=37), group 2; moderate COVID-19 severity patients (n=78), group 3; mild COVID-19 severity patients (n=159). Serum levels of C-reactive protein, D-dimer, and ferritin were measured in the three patient groups, and the patients were subjected to CT chest imaging.  Serum levels of the tested biomarkers were measured by ELISA at diagnosis. Results: Sever COVID-19 patients had higher serum levels of ferritin and D-dimer in comparison to patients with moderate and mild severity COVID-19 with statistically significant difference (p < /em> value 0.01 and 0.02 respectively). There was a significant elevation in the serum levels IL-6 and TNF-α in severe COVID-19 patients (488.5±112.2 and 159.6±38.3 respectively) versus moderate (206.07±53.3 and 93.5±39.5) and mild group (200.9± 52.27 and 52.9±23) respectively, (p < /em> value < 0.001). There was also a significant elevation of C5b and C5b-9 serum levels in severe COVID-19 patients (18.6±10.3 and 73.25±7.35) compared to moderate (14.11±15.6 and 143.6±170) and mild COVID-19 groups (76± 11.32 and 3.9± 3.03) respectively. Conclusion: We conclude that the severity of inflammation presented in elevated neutrophil counts and serum levels of inflammatory cytokines IL-6 and TNF in association with sever complement activation are implicated in severity and bad prognosis of COVID-19.