To explore the relationship between the dynamic changes of lymphocytes in the early stage (within 72 hours of admission) and the severity of disease in patients with coronavirus disease 2019 (COVID-19). A retrospective study was conducted. The clinical data of COVID-19 patients admitted in Wenzhou Central Hospital from January 17, 2020 to February 14, 2020 were collected and analyzed. According to whether there was lymphopenia on the first day of admission [lymphocyte count (LYM) < 0.8×109/L], whether the difference between LYM on the third day and the first day of admission (ΔLYM) was less than 0, the patients were divided into four groups: the first group was LYM normal on the first day of admission, ΔLYM ≥ 0; the second group was LYM normal on the first day of admission, ΔLYM < 0; the third group was lymphopenia on the first day of admission, ΔLYM ≥ 0; the fourth group was lymphopenia on the first day of admission, ΔLYM < 0. The study endpoint was the development of severe/critically ill patients within 30 days after admission. Severe/critical standard referred to classification of Diagnosis and treatment protocol for coronavirus disease 2019 (trial version 5, revised edition). The differences in general information, laboratory results, and probability of developing severe/critical were compared among the four groups. Cox regression analysis was used to analyze the correlation between the early dynamic changes of lymphocytes and the probability of severe illness; and the Kaplan-Meier survival curve was drawn to assess the probability of severe illness in patients with different LYM groups. A total of 104 patients with COVID-19 were enrolled, and 21 patients developed to severe/critical cases within 30 days of onset (accounting for 20.2%; 17 severe cases and 4 critical cases). There were significant differences in age (F = 5.061, P = 0.003), white blood cell count (WBC) on the first day of admission (Z = 10.850, P = 0.013), C-reactive protein (CRP) on the first day of admission (Z = -4.449, P < 0.001), LYM on the first day of admission (Z = 43.132, P < 0.001), LYM on the third day of admission (Z = 40.340, P < 0.001), and the occurrence of severe/critical illness (χ2 = 18.645, P < 0.001) among the four groups. Patients in groups 3 and 4 were older; patients in group 3 had the lowest WBC and LYM on the first day of admission; patients in group 4 had the highest CRP on the first day of admission, the lowest LYM on the third day of admission, and high proportion of severe/critical cases. Regarding the probability of severe/critically ill patients within 30 days of admission, univariate Cox regression analysis showed that the probability of severe/critical patients in group 4 was 12.7 times higher than that in group 1 [hazard ratio (HR) = 12.732, 95% confidence interval (95%CI) was 3.951-41.025, P < 0.001]; age, CRP, albumin (ALB) and lymphocyte grouping were included in multivariate Cox regression analysis, the probability of severe/critically ill patients in group 4 was 6.4 times that of group 1 (HR = 6.398, 95%CI was 1.757-23.301, P = 0.005); however, there was no difference in the probability among the group 1, 2 and 3. Kaplan-Meier survival curve showed that the probability of severe/critically ill patients in group 4 was significantly higher than that in groups 1, 2 and 3 (Log-Rank test: χ2 = 42.617, P < 0.001). Early lymphocyte dynamics change is related to the severity of patients with COVID-19. Patients with low LYM on the first day and continued decrease within 72 hours of admission have a higher probability to develop into severe/critically cases.