The McMaster nuclear reactor (MNR) is an important research facility that not only provides researchers with neutrons for fundamental science, but also supplies the medical industry with isotopes used for cancer treatment. To ensure the safety and performance of the MNR, modeling of the thermal hydraulics during nominal and accidental conditions is required. For such a task, system codes are customarily used. While system codes can assess the safety aspects of complex thermal–hydraulic systems, the question arises whether such systems can be modeled appropriately in a three-dimensional manner, such as computation fluid dynamics (CFD), while capturing the thermal mixing of the coolant. Modeling the thermal hydraulics of nuclear research reactors using CFD is relatively new. Therefore, validating such methods against experimental data is of utmost importance. The validation of CFD is the main focus of this work. More specifically, the influence of the loss of heat sink on the pool temperature is assessed using the CFD code Ansys CFX. The validation basis was provided by an experiment performed at the MNR in March 2023. In this experiment, the secondary heat removal system was intentionally shut down, and the pool temperature was measured in a few positions. The results obtained by modeling the loss of heat sink in the MNR using Ansys CFX agree well with the experiment.