The immunomodulation occurring in human transfusion medicine is thought to be a result of the leukocytes (WBC) present in blood components, and leukodepletion (LD) which is the reduction of WBCs from blood components is suggested for several blood transfusion (BT) situations. However, the probable effects of BT on the canine immune system are insufficiently known. In this manner, the presented study investigated the effects of WBC reduced compatible packed red blood cell (pRBC) transfusion on the canine immune system of the recipients. A complete blood count (CBC) and a differential count have also been performed. The immune system of recipient dogs were investigated on different blood withdrawal days (0, 10, 21, 31, and 42) for CD3+, CD4+, CD8+, CD45RA+, CD4+CD45RA+ T lymphocytes and CD4/CD8 ratio by using flow cytometry methods. The differences observed between groups and days for the investigated immunological and hematological parameters were not of statistical significance. With the exception of CD3+ T lymphocytes, which decreased on day 42 compared to days 0, 10 and 31 (p < 0.05). Moreover, the total WBC count in CBC and the percentage of lymphocytes on differential WBC count, both decreased in the WBC containing group compared to the WBC reduced group (p < 0.05). Mean corpuscular volume (MCV) and hemoglobin concentration parameters decreased in the recipients receiving WBC reduced pRBCs (p < 0.05). MCV was also statistically higher on day 21 compared to the rest of the days (p < 0.05). We found that the immune system of healthy mongrel dogs did not react profoundly different to the pRBC transfusion whether it was WBC reduced or not. Although, we have found that two consecutive compatible pRBC transfusions led to a statistically significant decline in CD3⁺ T lymphocytes, and a suppression of total WBC count and lymphocyte percentage in recipients receiving pRBC with WBCs. In conclusion, the mild changes observed in the immune system are yet far away of concluding an immunosuppressive effect of BT in healthy dogs. Nevertheless, this study may provide the possibility to understand the immune answer that takes place towards blood products containing WBCs. On the other hand, long-term follow up and higher units of pRBC transfusions are suggested for further understanding of the immunomodulatory effects related to BT. Furthermore, WBC's transfused in blood products might have different consequences in ill patients since they are often immunocompromised.