A comprehensive numerical study of air flow and thermal management of data centers is conducted for different plenum depths, tiles perforation ratios and rack power densities. Temperature/air flow profiles and data centers thermal management are quantified using the performance measuring parameters SHI (Supply Heat Index), RHI (Return Heat Index) and RTI (Return Temperature Index). A CFD (Computational Fluid Dynamics) approach for air flow and temperature distribution simulation in the data centers is used. The results showed that increasing the plenum depth: (i) increases the uniformity of air flow rate in the data center, (ii) increases the possibility of recirculation of hot air at the racks tops and bypass of cold air at the sides of the terminal racks of the racks row, and (iii) changes the values of the measurable performance parameters to be outside the recommended ranges. The results recommend that a perforated tiles opening ratio of 25–30% and a plenum depth of 60 cm can be considered as the more suitable values for the data centers.