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Objectives: Recent studies after the outbreak of coronavirus disease 2019 have shown an association of the ABO blood group to the susceptibility of severe acute respiratory syndrome coronavirus 2 infection. Anti-A and anti-B antibodies, carbohydrate clustering, interleukin-6 levels and host transmembrane protease serine subtype 2 were suggested to cause the variable susceptibility of severe acute respiratory syndrome coronavirus 2 infection to the ABO blood groups. This study aims to find the association of the ABO blood group with severe acute respiratory syndrome coronavirus 2 infection susceptibility in Nepal. Methods: Population-based matched case–control study was conducted from October 2021 to February 2022 in Rupandehi district of Nepal. A total of 1091 reverse transcription-polymerase chain reaction confirmed coronavirus disease 2019 cases and 2182 controls were included in the study by convenient sampling method. Results: A statistically significant association of severe acute respiratory syndrome coronavirus 2 infection was observed for the blood group AB between cases and controls (11.5% vs 8.5%; odds ratio = 1.4, 95% confidence interval = 1.10–1.78). However, there was no association of severe acute respiratory syndrome coronavirus 2 infection for blood group A (26.7% vs 28.23%; odds ratio = 0.93, 95% confidence interval = 0.79–1.09), B (26.9% vs 29.84%; odds ratio = 0.86, 95% confidence interval = 0.73–1.02) and O (34.9% vs 33.41%; odds ratio = 1.07, 95% confidence interval = 0.92–1.25). Conclusion: This study reported slightly more susceptibility to severe acute respiratory syndrome coronavirus 2 infection among individuals with blood group AB.