Sysmex XE-5000 offers the body fluid modus which provides the opportunity to count and differentiate leukocytes in body fluids and cerebrospinal fluid (CFS). In this study, we evaluated the basic performance of this application using routinely obtained samples in comparison with manual counting. Reproducibility study yielded good results in samples with a high white blood cell (WBC) count, whereas relatively high imprecision was observed at low WBC counts. Linearity was established up to 1,500 cells/microL in CFS and 5,600 cells/microL in body fluid. The cell count by XE-5000 was highly correlated with that of the microscopic reference method. Highly fluorescent body fluid cells percent (HF-BF%) was observed in samples with tumor cells or activated macrophages, which provides information about the possible presence of tumor cells. In conclusion, total and differential WBC counts in body fluid and CFS can be reliably determined by XE-5000 in samples with increased cell counts. XE-5000 also provides screening information about the presence of tumor cells for further manual examination.