Purpose: To analyze the causes and countermeasures of poor white blood cell filtration in whole blood from a nursing perspective. Methods: Research time: January 2023 to June 2023, research subjects: 76 blood donors who donated whole blood at the Red Cross Blood Center. After grouping according to the computer randomization method, the final results showed that they were divided into a control group and an intervention group of 38 cases each. The control group adopted routine nursing procedures, and the intervention group implemented targeted nursing intervention to explore the effects of the intervention in the two groups. Results: The poor filtration of leukocytes from whole blood was mainly due to donor factors such as nervousness of blood donors (32.89%) and poor venous conditions (21.05%); operational issues such as puncture technology (28.95%) and insufficient anticoagulation (25.00%); and equipment factors such as filter quality (10.53%). Compared with the control group, the intervention group had shorter filtration time, lower leukocyte residual volume, and lower blood scrap rate (2.63% vs. 18.42%), comparison p < 0.05. The clot-free rate of samples in the intervention group was 63.16%, while only 26.32% of the samples in the control group were clot-free, and no grade 3 clots occurred. Comparison p < 0.05. Conclusion: The application of targeted nursing intervention can effectively improve whole blood filtration efficiency and reduce clot formation, providing a practical clinical practice path for improving the quality of blood products.