Ocean models are increasingly able to synthesize a large temporal domain with fine spatial resolution. With this increase in functionality and availability, ocean models are in high demand by researchers, establishing a critical need for validating a model’s ability to represent interior ocean dynamics. Satellite measurements are typically used for validation, however these measurements are limited to the upper layers of the ocean and therefore satellite measurements of sea surface height and sea surface temperature are the most validated output parameters of three-dimensional ocean models. Unfortunately there is a paucity of model validation studies for the interior ocean. This study fills a knowledge gap by contrasting model data from the Hybrid Coordinate Ocean Model (HYCOM) for the interior ocean in the Tongue of the Ocean (TOTO), Bahamas and the Gulf of Mexico (GoM) against observational (i.e., in situ) data collected in both locations. Conductivity temperature and depth (CTD) data in the GoM were collected during five research cruises by the DEEPEND Consortium between May of 2015 and May 2017. These data were collected as part of the investigation into the impact of oil spills on faunal communities in deep water of the GoM. CTD and expendable CTD (XCTD) data in the TOTO were collected by the Naval Undersea Warfare Center (NUWC) detachment Atlantic Undersea Test and Evaluation Center (AUTEC) in support of U.S. Navy acoustic testing between 1997 and 2017 to characterize the sound velocity profile of the water column. The global 1/12° HYCOM configuration (GLBu0.08) was found to be a better fit in the upper 400 and 250 meters of the TOTO for temperature and salinity, respectively, than the GoM 1/25° HYCOM configuration (GOMI0.04 1/25°) fit the GoM in situ data for the same depths. The GoM 1/25° HYCOM configuration (GOMI0.04 1/25°) provided a better fit in the GoM for depths of 500 and 300 meters and deeper for temperature and salinity, respectively, than the global 1/12° HYCOM configuration (GLBu0.08) fit the TOTO in situ data at the same depths. A comprehensive comparison of the vertical profile between the model and observational data for each of the regions of interest provides insight into using HYCOM forecast data for future applications.