Particle tracking of rigid fluorescent particles in microcirculation environments is often found to be difficult, since the presence of red blood cells (RBCs) at physiologically relevant conditions (i.e., hematocrit) masks the particle images. In turn, making particle detection challenging. To overcome this difficulty, we propose to use ghost RBCs for enhanced particle detection. These are quasi-transparent RBCs obtained by removing the hemoglobin from normal RBCs. To understand whether the ghost RBCs can improve the particle detection, we performed defocusing particle tracking measurements with the general defocusing particle tracking (GDPT) method of the rigid fluorescent particles in normal and ghost RBC flows. The measurements were performed at physiological relevant hematocrit and for three different flow rates. From the three-dimensional particle trajectories, we evaluated the correlation coefficient from the GDPT evaluations and compared the fluid dynamic behavior of the two types of cells. Overall, the results show that ghost RBCs are an attractive solution for this type of experiments, since they improve the correlation coefficients up to values similar to cell-free experiments, while exhibiting a fluid dynamic behavior similar to normal RBCs i.e., in terms of velocity and relative viscosity data.