COVID-19 is a contagious globally threatening infectious disease that accounted for an ongoing pandemic that manifested in multi-organs diseases and failures. In the current study, a cross-sectional investigation was conducted using an untargeted metabolomics-based approach to identify metabolomic alterations and their relationship to immune pathways in Pfizer (a high efficacy and protective vaccine) and Sinopharm (low effectiveness and protection rate) vaccinated participants to investigate vaccines effectiveness. Plasma samples were collected from non-vaccinated participants (n=77), Sinopharm vaccinated participants (n=107), and Pfizer-vaccinated participants (n=156) who met the inclusion criteria for the study. Comparative metabolomic analysis using TIMS-QTOF. One-way ANOVA test using MetaboAnalyst Software was conducted, out of 105 detected metabolites, 72 were statistically significant (p<0.05). Metabolites such as Neopterin, pyridoxal, and syringic acid were highly altered with Pfizer-vaccinated individuals while sphinganine, neopterin, and sphingosine were impacted due to Sinopharm vaccination which might be the potential biomarkers for vaccine efficacy. Furthermore, Pfizer and Sinopharm vaccination had altered sphingolipid metabolism pathways and histidine metabolism pathways when compared to control and when comparing the two vaccines together. The Sinopharm group exhibited altered lysine degradation when compared to the control group. Comparing the enriched pathway of Pfizer and Sinopharm groups, purine metabolism was affected. Comparing the Pfizer group with the controls and Sinopharm revealed perturbations in tryptophan metabolism and vitamin B6 metabolism. More studies are needed using more than one cohort and to compare dual vaccinated individuals to verify the implication of the above metabolites on immune responses and their value in the protection and effectiveness of vaccines.