Background COVID-19 is an ongoing pandemic posing a big threat to public health and economy. Novel variants are constantly emerging with different transmissibility and pathogenicity. This study aimed to explore the hematological characteristics of COVID-19 delta variant during the outbreak in July 2021, Nanjing. Methods This study retrospectively analyzed demographic and clinical parameters of 80 patients diagnosed with COVID-19 delta variant infection. Patients were classified into mild, moderate and severe/critical group according to the guideline. Characteristics of each group were compared. Results The percentage of elderly and patients with comorbidities was significantly higher in the severe/critical group. Vaccination rate was significantly lower in this group. Decreased lymphocyte number, especially CD4+ and CD8+ T cells, elevated fibrinogen, CRP, PCT and IL-6 were associated with disease severity (P<0.05). Severe or critical cases tended to have higher viral load shown by lower CT values of ORF1ab and N gene (P=0.08, P=0.06) and lower specific IgG antibody level (P=0.15) but it did not reach statistical significance. Conclusions Increasing vaccination rate in the elderly and population with comorbidities might improve the prognosis of COVID-19 delta variant. Mechanism study of immune evasion of COVID-19 and methods to booster our immune system was urgently needed.