In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. Total lymphocytes, CD4⁺ T cells, CD8⁺ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8⁺ T cells and CD4⁺/CD8⁺ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8⁺ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8⁺ T cells and B cells and increase in CD4⁺/CD8⁺ ratio were indicated as independent predictors of poor efficacy. Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8⁺ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.