Objective To evaluate the value of Sysmex XT-4000i hematology analyzer in its body-fluid mode in cell count and cell differential count of pleural effusion, ascites and cerebrospinal fluid samples. Methods A total of 95 pleural effusion, ascites and cerebrospinal fluid samples were collected from patients hospitalized between May and September 2015. The samples were tested by Sysmex XT-4000i hematology analyzer (instrument method) and modified Neubauer hemocytometer (manual method) for cell count, and the results of them were compared and analyzed. Results The instrument method and the manual method had a good consistency in nuclear cell count and erythrocyte count (kappa=0.965,P< 0.001; kappa=0.988,P<0.001). There was no significant difference in the count of mononuclear cells (P> 0.05). However, there was a significant difference in the count of multiple nuclear cells (P<0.05). Conclusions Hematology analyzer in its body-fluid mode may replace manual method in cell count of pleural effusion, ascites and cerebrospinal fluids for its high precision, high efficiency and easy operation. However, cell differential count of this method needs microscopic examination assistance.