White blood cells (WBCs) reside close enough to the endothelium vascular wall to detect a variety of chemical signals and combat bacterial and viral diseases in the human body. It is vital to understand the phenomenon of WBC margination since it is an essential mechanism in microcirculation which aids fighting infections. Several factors influence WBC margination, including hematocrit (Hct), flow rate, red blood cell aggregation, red and white blood cell deformability, and the width of red blood cell free layer. WBC dynamics is strongly influenced by the presence of RBCs. In this study, we investigate WBC margination by varying the size and shapes of RBCs. The change in size and shape of RBCs is achieved by altering the tonicity of the blood sample. The margination phenomenon is studied at different values of hematocrits (3% and 19-22% Hct) and flow rates (0.2-1 μl/min). The different values of hematocrits is achieved by diluting the whole human blood using normal saline (0.9% NaCl), hypotonic saline (0.45% NaCl), and hypertonic saline (3% NaCl) solutions, respectively. Experiments are conducted using three different geometrical microchannels; straight, curved, and constriction-expansion (CE). The findings of hypotonic and hypertonic saline solutions are compared to the results of normal saline solutions. It is found that hypotonic and hypertonic solutions have minimum effect on WBC margination in a curved channel; however, in the case of straight and CE channel margination improves. When blood cells are diluted with hypotonic saline, WBC margination is shown to be highest in constriction-expansion microchannels, whereas for straight microchannel, the hypertonic solution provides the best margination. We also report particle dynamics within the microchannel and compare their behavior with experimental results for Hct 3%. This study provides critical information on WBC margination in situations where RBCs deviate from their normal shape and size.