Leukodepletion of whole blood-based perfusates remains a challenge in experimental models of ex vivo perfusion. This study investigated the leukoreduction efficacy of the commonly used LeukoGuard LG Arterial and BC2 Cardioplegia filters. Eleven liters of washed porcine blood was used to evaluate the filtration efficiency of LG (n = 6) and BC2 (n = 5) filters. Filter efficacy was tested by passing 1 L of washed blood through each filter. Complete blood count was performed to detect a reduction of white blood cells, red blood cells, and hemoglobin concentration. The BC2 Cardioplegia filter showed a significant reduction in white blood cell count (13.16 ± 4.2 × 103 cells/μL pre-filtration, 0.62 ± 0.61 cells/μL post-filtration, p = 0.005), red blood cell count (9.18 ± 0.16 × 106 cells/μL pre-filtration, 9.02 ± 0.16 × 106 cells/μL post-filtration, p = 0.012) and hemoglobin concentration (15.89 ± 0.66 g/dL pre-filtration, 15.67 ± 0.83 g/dL post-filtration, p = 0.017). Platelet reduction in the LG filter group was statistically significant (13.23 ± 13.98 × 103 cells/μL pre-filtration, 7.15 ± 3.31 × 103 cells/μL post-filtration, p = 0.029), but no difference was seen in the BC2 group. There was no significant difference in white blood cell count in the LG filter group (10.12 ± 3.0 × 103 cells/μL pre-filtration, 10.32 ± 2.44 × 103 cells/μL post-filtration, p = 0.861). Our results suggest that the LG filter should not be used in ex vivo perfusion circuits for the purpose of leukodepletion. The BC2 filter can be used in EVP circuits with flow rates of less than 350 mL/min. Alternatively, perfusate may be leukodepleted before perfusion.