Vapor pressure deficit (VPD) can be used as an indicator to schedule greenhouse irrigation. VPD can be estimated as a function of relative humidity (RH) and temperature (T). The objective of this work was to analyze spatial variation in VPD as an indicator of water stress influenced by concentration of water vapor and intensity of near infrared (NIR). The study was carried out in an empty three-span sawtooth greenhouse with natural ventilation under the local climate in Montecillo, Mexico; these findings established a base value to analyze greenhouse field conditions prior to the influence from a crop. The experimental phase consisted of recording data (3 February 2019–24 February 2019) on temperature, humidity, solar radiation, and wind speed, which were used for developing a model in computational fluid dynamics (CFD). Then, this model was used to estimate VPD, considering changes in mass fraction of water vapor and the intensity of NIR. Scenarios with 50, 70, and 90% external RH were evaluated. It was found that without a crop, temperature was not affected by the variation in the mass fraction of water vapor and the intensity of NIR in the simulated scenarios, each of which generated a thermal gradient within the range of 4 °C. When considering the scenario of 90% external RH, we found the best VPD range along the greenhouse (2–3 kPa) that would be a favorable field condition for crops. Differences between VPD with and without a crop can be used to estimate the water quantity needs for crop growth based on the climate variables examined in this study, where higher VPD values require more water for irrigation.