Creating a micro-environment around infected occupants constitutes an effective strategy in reducing contaminants spread insuring a relatively clean macroclimate decreasing the risk of infection for occupants circulating in an office space. In this work, the ability of ceiling personalized ventilation (CPV) system assisted by desk fans (DF) or chair fans (CF) was studied with respect to confining contaminants spread in typical office space while considering possible occupant shift. A 3D computational fluid dynamics (CFD) model was developed to simulate particle spread. The developed model was validated experimentally with respect to concentration values using a thermal manikin in a climatic chamber with controlled particle generation. A parametric study was followed to determine the effect of the occupant shift from CPV design position, the CPV+DF or CF configuration, and the canopy angle on confinement performance for minimal particle spread in the space. The CPV jet and diffusers’ flow canopy favored particle deposition within the microclimate region leading to their removal from indoor air. For no occupant shift, assisting the CPV jet by DF or CF was very efficient in particle confinement. However, in the cases of critical backward occupant shift, flow asymmetry was formed around the occupant leading to particle spread and leading to asymmetry attenuation when operated with CF. The highest particle confinement was obtained for a canopy angle of 45° for the case of CPV assisted by CF due to forming a recirculation zone between the CPV and jet diffusers; hence trapping particles and reducing their spread to the macroclimate. It was found that a total supply flow rate of 60 L/s for MV is required compared to 43.5 L/s for the optimal CPV design, for equivalent average particle concentration within the macroclimate zone at the critical generation plane, leading to 62% reduction in power consumption of the supply fan.