Background: One of the zoonotic illnesses, COVID-19, is spreading from person to person by a variety of methods, including coughing, sneezing, or speaking, which spreads tiny droplets from the infected person's lips or nose . Corona virus vaccination generally causes modest side effects that become more noticeable after the second dosage. Creatine kinase (CK) is a protein that catalyzes the transfer of a phosphate group from creatine phosphate to adenosine diphosphate. Aim: This study aimed to compare between the impact of Pfizer vaccination and covid-19 infection on human creatine kinase activity and its isoenzymes. Patients and methods: (150) blood samples; one hundred blood specimens were collected from Covid-19 patients who attended to Al- Fallujah Teaching Hospital and Al-Razzi private hospital and, fifty Blood samples were collected from volunteers who attended to the vaccination outlets to be vaccinated with the Pfizer vaccine in Al- Fallujah Teaching Hospital. The study was conducted through the period from September 2021 to December 2021. Results: In the COVID-19 group of patients, there was a statistically significant difference (P < 0.05) in the mean levels of basal Total CK, basal CK-MB, and CK-MM in comparison with the vaccinated group. There was no statistically significant difference in mean of total CK after second dose between the two groups. There was a statistically significant decrease in mean of CK-mb and CK-mm in vaccinated group in comparison with COVID-19 group. Conclusion: Covid-19 infection had more impact on CK-MB and CK-MM than the Pfizer vaccination.The activity of CK-MB and CK-MM after covid-19 infection were higher than activity after Pfizer vaccination and before vaccination