Objective There is a probability that vaccination may lead to reduction in the severity and complications associated with COVID-19 infection among hospitalized patients. This study aimed to determine the characteristics, clinical profiles, and outcomes of COVID-19 infection in vaccinated and non-vaccinated patients. Design and data sources This prospective observational cohort study was conducted at the Aga Khan University Hospital (AKUH) and recruited COVID-19 patients admitted between June 1st and September 30th, 2021. Patients’ demographics, date of admission and discharge, comorbid conditions, immunization status for COVID-19 infection, presenting complaints, lab workup and computed tomography (CT) scan findings were obtained from the medical records. The primary outcome of the study was patients’ condition at discharge and the secondary outcomes included level of care, length of stay (LOS), requirement of non-invasive ventilation (NIV) and inotropic support. Results Among a cohort of 434 patients, 37.7% (n = 164), 6.6% (n = 29) and 55.5% (n = 241) were fully vaccinated, partially vaccinated, and unvaccinated, respectively. Around 3% and 42.9% of the patient required inotropic and NIV support respectively; however, there was no discernible difference between them in terms of vaccination status. In case of unvaccinated patients there were significantly increased number of critical care admissions (p-value 0.043). Unvaccinated patients had significantly higher median serum procalcitonin, ferritin, LDH and D-dimer levels. Around 5.3% (n = 23) of the patient required invasive ventilation and it was more common in unvaccinated patients (p-value 0.04). Overall, mortality rate was 12.2% (n = 53) and this was higher (16.2%, n = 39) in unvaccinated patients as compared to fully vaccinated patients (6.1%, n = 10, p-value 0.006). Conclusions Through this preliminary data, we can conclude that patient can develop severe and critical COVID-19 infection despite being vaccinated but this proportion is low as compared to unvaccinated population. So, uninterrupted endeavors need to be done to vaccinate as many individuals as possible. Furthermore, more effective vaccinations need to be developed to lessen the high death toll of COVID-19 infection.