Aim: The rapid global spread of the novel corona virus SARS-CoV-2 has strained healthcare and testing resources, making the identification and prioritization of individuals most at-risk became a critical challenge. Recent evidence suggests blood type may affect the risk of severe COVID-19.Method: In this cross-sectional observational study, among 1348 admitted patients in Holy Family Red Crescent Medical College who tested positive for RT-PCR, 294 patients were included with known blood type to assess the association between ABO and Rh blood types and demographic profile, co-morbidities, clinical outcomes, and changes in the biomarkers. Result: among 294 patients admitted to the hospital with COVID-19, the mean age was 48 to 49 years. Out of all patients, 211 were male, and 83 were female, with a ratio of 1: 2.54. The highest numbers of patients were between 50-59 years. The highest percentage of diabetic patients were present in the AB blood group (54%), and hypertensive patients in the O and Rh-negative blood group (40.29%, 60%) which were statistically not significant. Other than that, COPD, IHD, and CKD were observed. Symptoms of patients were categorized as inflammatory and neurological. Shortness of breath (52.41%), fever (38.43%), and cough (28.23%) were observed among inflammatory symptoms, which were statistically significant and lethargy (16.25%) was only remarkable neurological involvement. Among all ABO blood groups, 'A' blood group of patients, present with a higher percentage of both inflammatory and neurological symptoms. Among the Rh blood group, Rh-negative patients did not present with diarrhea, sore throat, lethargy, anosmia, and loss of taste. Changes in biomarkers levels were also observed in all blood groups. Conclusion: COVID-19 patients with blood group A or B are at increased risk of disease severity with the highest number of co morbidities and symptoms compared with patients with blood group O or AB.