Safe and effective whole-population vaccination against severe acute respiratory syndrome coronavirus 2 is the long-term solution to the ongoing coronavirus disease 2019 pandemic. Administration of COVID-19 mRNA vaccine induced a rapid onset of multifocal myopericarditis predominantly after the second dose of mRNA COVID-19 vaccines (Pfizer-BioNTech). However, the underlying mechanisms for development of myocarditis are not clear. The current study aims to identify the effect of Pfizer vaccine on the cardiac function in male rats and to explore the underlying mechanisms for the disturbed cardiac function. 22 adult male Wistar rats were allocated to 2 groups. Control group were injected with normal saline, and Pfizer-injected group received 2 doses of Pfizer vaccine intravenous. Two weeks later, recording of ECG was done and rat hearts were isolated and perfused using Langendorff preparation, in addition, blood sampling was done. Significant bradycardia and significant decrease in the peak tension was demonstrated. In addition, significant prolongation of time to peak tension, half relaxation time and contraction time were reported. Biochemical findings revealed significant increase in cardiac tissue Interleukin-18, Interleukin -6, Tumor necrosis factor-alpha and cardiac malondialdehyde. This was accompanied by significant increase in plasma D-Dimer, cardiac troponin, C-reactive protein and cardiac catalase. Histological findings showed marked apoptotic cardiac muscle fibers. Therefore, Pfizer vaccine injection impaired the cardiac muscle function through myocardial inflammation, apoptosis and increasing myocardial oxidative stress