Abstract Background Low titer group O whole blood (LTOWB) use across the United States is increasing. This simulation calculated the number of female donors who would qualify for LTOWB donation if HLA‐antibody screening was implemented in different strategies. Methods Using US nativity data and information on blood donors from 2023, a model was constructed that calculated how many of these donors would be males and nulliparous females, neither of which require HLA‐antibody screening before LTOWB donation. The model then calculated how many parous females would be HLA‐antibody sensitized based on each woman's parity in three antibody screening scenarios: all parous women, all parous women ≥50 years old, and all parous women older than the 99th percentile of the age of final birth. These calculations were performed for RhD‐negative and RhD‐positive donors. Results The model calculated that there would be 222,239 RhD‐negative male and 74,655 nulliparous RhD‐negative female donors. If all group O RhD‐negative parous females were screened, 109,479 were calculated to not be HLA‐sensitized for a total of 406,373 LTOWB eligible donors. If only the group O RhD‐negative females ≥50 years were screened, 59,138 donors would not be HLA‐sensitized for a total of 356,032 LTOWB eligible donors. If only the group O RhD‐negative females ≥42 years, the 99th percentile for last birth age, were screened, 80,375 donors would not be HLA‐sensitized for a total of 377,269 LTOWB eligible donors. Higher numbers of LTOWB donors were realized when RhD‐positive males and females were modeled. Conclusion HLA‐antibody screening realizes additional LTOWB donors.