Background: The covid-19 disease has caused many deaths worldwide since December 2019. Many thromboembolic events, such as VTE and TTP, have been reported since the beginning of this pandemic. Considering the prominent role of complement in developing TTP and TTP-like syndrome in recent studies, this study aimed to assess the prevalence of TTP-like syndrome and its relationship with complement activity in critically ill patients with COVID-19. Method: This study was conducted on 77 COVID-19 patients admitted to the ICU wards of Tabriz Imam Reza hospital from March to June 2021. TTP-like syndrome was diagnosed using a blood specimen for evidence of thrombocytopenia, microangiopathic hemolysis (low hemoglobin, increased LDH level, schistocytes in a peripheral blood smear, and negative direct agglutination test), and end-organ injury, including acute kidney injury or neurological deficit. ADAMTS 13 activity levels could not be achieved owing to logistic issues; therefore, we could not accurately diagnose TTP and TTP-like syndrome based on ADAMTS 13 levels, so to increase the accuracy of diagnosis, we have included people with classical pentad evidence in the TTP-like syndrome group. Complement parameters, including C3, C4, and CH50, were measured. Result: Seven cases of TTP-like syndrome were diagnosed using the previously mentioned criteria, which stands for 9.1% of the study population. Compared with patients without TTP-like syndrome, C3 was significantly lower in patients with TTP-like syndrome (p-value = 0.014), and C4 and CH50 demonstrated insignificant differences between the two groups (p-value = 0.46, p-value = 0.75). Conclusion: Our study showed that the TTP-like syndrome was present in a significant percentage of critically ill patients with COVID-19. Lower C3 levels in TTP-like syndrome-diagnosed patients can indicate complement activation as one of the influential factors in initiating TTP-like syndrome in COVID-19 patients. More studies are recommended to clarify the exact mechanism to achieve adequate therapeutic methods and better manage the disease and its complications.