Objective To investigate the charges of lymphocyte subset counts [CD4⁺ T cells, CD8⁺ T cells and natural killer (NK) cells] and the ratio of neutrophils to lymphocytes (NLR) in patients at the early phase of sepsis and its predictive values for the prognosis. Methods A total of 62 sepsis patients admitted to the First Hospital of Shanxi Medical University from December 2019 to December 2020 were included in this study. These patients were divided into survival group and death group according to their conditions of 28-day follow-up. T lymphocyte subsets, NK cell count, NLR, Acute Physiology and Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score at day 1 and 3 after admission were measured and recorded, and the relationship of these indexes with patient prognosis and their predictive values were analyzed. SPSS statistics 26.0 was used to perform the statistical analysis. Student′s t test, Rank sum test or Chi-square test was employed for intergroup comparison depending on different data types. Results Compared with the survival group, the death group had significantly higher APACHEⅡ and SOFA scores on both day 1 and day 3 (P<0.05), obviously lower counts of lymphocytes, T lymphocytes, CD4⁺ T cells, CD8⁺ T cells and NK cells on day 3 (all P<0.05), whose counts were negatively correlated with SOFA score (r=-0.19, -0.16, -0.17, -0.18, -0.26; P<0.05), and notably higher NLR (P<0.05), which was positively correlated with APACHEⅡ score (r=0.45, P<0.05). The area under receiver operating characteristic curve (AUC) for APACHEⅡ score, SOFA score, NLR, lymphocyte count, T lymphocyte count, CD4+ T cell count, CD8+ T cell count, and NK cell count on day 3 for predicting patient′s 28-day prognosis were 0.84,0.73,0.76,0.84,0.83,0.81,0.82 and 0.78, respectively. Conclusion Immunosuppression occurs in the early phase of sepsis. T lymphocyte subset counts, NK cell count and NLR show good predictive values for prognosis in septic patients.