Objective: To investigate the expression patterns and clinical significance of specific lymphocyte subsets in the peripheral blood of patients with SARS-CoV-2 infection. Methods: Between December 2022 and February 2023, a cohort of 199 patients from the First Affiliated Hospital of Guangzhou University of Chinese Medicine were analyzed. The participants represented various stages of coronavirus infection severity: mild, moderate, severe, and critical. Additionally, 40 healthy individuals constituted the control group. The FC 500MPL flow cytometer and associated reagents for flow cytometry. Results: Compared with the healthy control group, activated B lymphocytes witnessed a pronounced increase (p < 0.05). A significant decrease was observed in the levels of Breg, Tc/s, late activated T, late activated Th, and late activated Tc/s lymphocytes (p < 0.05). Th, initial Th, initial Tc/s, total Treg, natural Treg, induced Treg, early activated T, and early activated Th lymphocyte levels showed no significant difference (p > 0.05). As the disease progressed, there was an uptick in mid-term activated T lymphocytes (p < 0.05), while Breg, T, Tc/s, senescent Tc/s, and total senescent T levels dwindled (p < 0.05). Noteworthy patterns emerged across different groups for B1, T-lymphocytes, Tc/s, B2, CD8+ Treg cells, and other subsets, highlighting variance in immune responses relative to disease severity. When juxtaposed, no significant difference was found in the expression levels of lymphocyte subsets between patients who died and those deemed critically ill (p>0.05). Conclusion: Subsets of Treg and B-cells could act as yardsticks for the trajectory of SARS-CoV-2 infection and might have potential in forecasting patient trajectories. A comprehensive evaluation of lymphocyte subsets, especially in real-time, holds the key to discerning the clinical severity in those with COVID-19. This becomes instrumental in monitoring treatment outcomes, tracking disease evolution, and formulating prognostications. Moreover, the results provide a deeper understanding of the cellular immune defense mechanisms against the novel coronavirus infection.