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Regional variations are found in the incidence and severity of the COVID‐19 infection. Human leukocyte antigen (HLA) polymorphism is one of the genetic factors that might have an impact on the outcome of the disease. This study explored the association between the HLA genotype and the severity of COVID‐19 among patients from South Asia. Blood samples from 95 Asians (Bangladeshis, Indians, and Pakistanis) with COVID‐19 were collected. The patients were divided according to the severity of their infection: mild (N = 64), severe (N = 31), and fatal (N = 20). DNA was extracted from all samples, and HLA genotyping was performed for both class I (A, B, and C) and class II (DRB1, DQA1, and DQB1) using the PCR‐rSSO (polymerase chain reaction–reverse sequence‐specific oligonucleotide) molecular method. The frequency of HLA‐B*51 was significantly higher among patients in the fatal group than among those in the mild infection group (15% vs. 4.7%, p = 0.027). Additionally, the frequency of HLA‐B*35 was significantly higher in the mild infection group than in the fatal group (21.1% vs. 7.5%, p = 0.050 [a borderline p‐value]). In terms of HLA class II, DRB1*13 was significantly observed in the fatal group than in the mild infection group (17.5% vs. 11.3%, p = 0.049). However, the p‐value for all alleles became insignificant after a statistical correction for the p‐values (pc = 0.216, pc = 0.4, and pc = 0.49, respectively). Compared with all published data, this study highlights that the association between the HLA system and the COVID‐19 outcome might be ethnic‐dependent. Genetic variation between populations must be examined on a wider scale to assess infection prognosis and vaccine effectiveness. Research Highlights: HLA polymorphism might play a role in COVID19 infection.HLA polymorphism might be associated with COVID19 severity among South Asians. [ABSTRACT FROM AUTHOR]