Background: The most widely used vaccination against SARS-associated coronavirus (SARS-CoV-2) is the Pfizer vaccine, which provides protection against this virus. However, its ability to safeguard the oral cavity is unclear, and neither are the exact immunological biomarker levels it activates. This study aims to detect if the Pfizer-BionTech covid-19 vaccine protects the oral cavity after vaccination by estimating the salivary sIgA levels, IL-21 in saliva for subjects before and after vaccination with the Pfizer covid-19 vaccine. Methods: In this cross-sectional study, 70 subjects were followed up: the non-vaccinated individuals served as the control group, and those who received the first and second doses of the vaccine constituted the study group. The salivary biomarkers sIgA and IL-21 were detected using enzyme-linked immunosorbent assay (ELISA) kits. Results: The current study showed a highly significant (p=0.0001) in secretary-IgA levels after the first vaccination in follow-up compared with non-vaccinated in same subjects (as control), while a non-significant when compared with after second vaccination groups. However, salivary IL-21 levels showed highly significant differences between the non-vaccinated follow-up comparing with after first and after second vaccination also compared the first with second followed up groups reflect an increased and highly significant difference (p<0.001). Conclusion: The current study shows that the Pfizer vaccine has a minimal impact on sIgA levels due to its primary role in systemic rather than local salivary protection. However, a rise in IL-21 was observed after the first dose in non-infected participants, indicating its systemic protective effectiveness, which stabilizes after the second dose.