This paper describes a methodology for coupling an advanced model of the thermo-regulatory system of the human body that describes its physiological processes, a comfort model that evaluates thermal sensation and comfort, and the ESP-r building simulation software that computes the transient thermal response of a building model. The objective of this study was to utilise the physiology and comfort models to dynamically modify the heating and cooling temperature set points of a zone controller in ESP-r, in accordance with the computed human thermal sensation and achieve realtime thermal comfort management. The comunication between the software is managed by the ESP-r controller, which at each simulation time step prints the building states on text files. The building states are then used by the physiology and comfort models to compute the perceived sensation and comfort metrics. These metrics are utilised by a logic in the controller of the indoor conditions to calculate the temperature set point corrections for the next time step. Simulation results were generated for a single zone model, using UK climate, over five winter and five summer days. Both winter and summer tests showed the expected behaviour in set point modification. The integration of the comfort model during the simulation of the case study building shows promising results in adjusting the set point by maintaining a relatively wide temperature range that ensures the building does not utilise excessive energy to maintain a narrow comfort band and at the same time that local thermal comfort requirements are satisfied.