Statistics show that most fires occur in civil residential buildings. Most casualties are due to the inhalation of hot air loaded with smoke, leading to intoxication with substances harmful to the human body. This research aimed to develop a CFD model that relates the operation of the sprinkler system to the operation of the ventilation system through the air temperature in a specific point close to the sprinkler position. A real-scale experiment was carried out, and a CDF model was developed. Several parameters of the CFD model (thermal conductivity of the experimental test room walls, numerical grid elements’ dimensions, burner heat release rate variation) were imposed to the model, so that the resulting entire time variation of the temperature next to the sprinkler location corresponds to the real measured variation. Two other experiments were used to validate the numerical model. Besides the air temperature, at this point, other essential parameters were determined in the entire experimental space: indoor air temperature, visibility, oxygen concentration, and carbon dioxide concentration. We found that if the ventilation rate increases, the indoor temperatures in that specific point decrease, and the sprinkler is activated later or, in some cases, it might never be activated. However, this conclusion is not valid for the entire analyzed space, as the ventilation system alongside the natural air movement imposes specific air speed and specific temperature distribution inside the analyzed space.