Removal of heat is becoming a major challenge in today’s data centers. Computing-intensive applications such as artificial intelligence and machine learning are pushing data center to compute intensive systems, such as GPU, CPU, and switches to their extreme limits. Racks of IT can approach up to 100kW of heat dissipation challenging traditional data center designs for enterprises and cloud service providers. Direct-to-chip liquid cooling utilizing cold plates is becoming a common method of removing heat from high heat density data center server racks. There are various methods of applying liquid cooling to data centers to address the high heat density components such as liquid to liquid (L2L), liquid to air (L2A), and liquid to single phase refrigerant (L2R). This study aims to investigate the thermo-hydraulic performance of the L2L cooling systems using cooling distribution units (CDUs). CDUs provide a cold secondary coolant (Propylene Glycol 25%) into the cooling loops of liquid-cooled server racks, with the CDUs providing liquid to liquid heat exchange between the primary facility water and secondary liquid used for cold plates. This study uses Thermal Test Vehicles (TTVs) which have been built to reproduce and simulate high heat density servers. Four different cooling loops are characterized experimentally, and detailed analytical and numerical simulations using CFD are developed for analyzing the cooling characteristics of the entire L2L cooling loop, including the CDU, for removing heat from the cold plates. Detailed Flow Network Modeling (FNM) has been performed to analyze precise hydraulic modeling of the secondary fluid flow, from the CDUs to the cooling loops, for predicting pressure drop and flow rate of the secondary coolant. A FNM properly sizes the pumping requirements of the L2L cooling system. Additionally, a system calculator has been created for quickly sizing all secondary loop piping for L2L heat exchanger deployments.