The contribution of B cells in COVID-19 pathogenesis, beyond the production of specific antibodies against SARS-CoV-2, is still not well understood. Since one of their most relevant functional roles includes their immune-suppressive mechanisms, we decided to evaluate one of the most recognized human B regulatory subpopulations: the IL-10⁺ B10 cells, during COVID-19 onset. After stimulation of PBMCs for IL-10 induction, we employed multiparametric flow cytometry to determine B10 frequencies in severe and critical COVID-19 patients and then correlated those with clinical and laboratory parameters. Compared with healthy individuals, we detected a significant reduction in the B10 subset in both patient groups, which correlates with some inflammatory parameters that define the disease severity. This evidence suggests an aberrant role of B10 cells in immune responses against SARS-CoV-2 that needs to be further explained.