Introduction: The characteristics of leukopenia in patients with systemic lupus erythematosus (SLE) in different studies are different, which may be related to region, race, and sample size. Moreover, the extent of leukocyte count decline remains to be studied. This study aimed to analyze the clinical characteristics of leukopenia in patients with SLE of Han ethnicity in China. Methods: A single-center, retrospective, crosssectional study was conducted in Chinese Han patients with SLE from June 2013 to August 2020. Results: A total of 125 patients with SLE were included in the study, and 104 age-and sexmatched healthy controls were recruited. The prevalence of leukopenia, neutropenia, and lymphopenia was 40.0, 20.8, and 55.2%, respectively. The median leukocyte count in the leukopenia group was 2.80 9 10 9 /l, the median neutrophil count in the neutropenia group was 1.40 9 10 9 /l, and the median lymphocyte count in the lymphopenia group was 0.60 9 10 9 /l, which was 47.06, 40.58, and 30.00% of the median of the healthy control group, respectively. The lymphocyte count of SLE patients without lymphopenia was also lower than that of healthy controls, and the lymphocyte count was negatively correlated with the SLE disease activity index 2000 score in all patients with SLE. Independent risk factors for neutropenia include decreased platelet count and lymphocyte count, as well as the presentation of cylindruria. For lymphopenia, the independent risk factors were positivity for anti-dsDNA antibody and Coombs' test, decreased platelet count, and cylindruria. Conclusions: In Han Chinese patients with SLE, leukopenia, neutropenia, and lymphopenia are common clinical manifestations, and the degree of reduction in blood cell count was also remarkable. Lymphopenia is associated with disease severity in patients with SLE. The correlation between Coombs' test results and lymphopenia deserves further study.