The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-d/pre-o donor units obtained before March 2021, 20 post-d COVID-19/postvaccination units, and 1 pre-d/pre-o hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], d, and o) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to d or o, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-d COVID-19/postvaccination units and the