In 2020, the SARS-COV-2 disease (COVID-19) imposed huge challenges on the health, economic, and political systems, and by the end of the year, hope had been born with the release of COVID-19 vaccines aimed at bringing the pandemic to an end. However, the COVID-19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy, vaccine-induced thrombotic thrombocytopenia, and leukocytoclastic vasculitis, after receiving the ChAdOx1 nCoV-19 vaccine. Therefore, it is critical to investigate and report the occurrence of adverse reactions following vaccination, particularly serious ones, as it contributes to the growing body of research and assists clinicians in better diagnosing and managing them.