Our literature review on demand response reveals a predominant focus on electricity demand reduction, with limited attention to occupants’ thermal comfort, which is often assessed under steady-state conditions. To address these gaps, this study uses Computational Fluid Dynamics (CFD) simulations to assess thermal comfort during response and recovery periods of global temperature adjustment. Two ventilation strategies—mixing and displacement—were investigated under three internal load intensities (low, medium, and high) in the U.S. Department of Energy (DOE) reference small office building. Overall thermal comfort was assessed using predicted mean votes (PMVs) and the one-time constant, while local discomfort was evaluated based on ankle-level temperature, vertical temperature gradient between head and ankle, and draft risk. Results show that displacement ventilation adjusts temperatures in the ASHRAE breathing zone 45%–48% faster during the response period and 51%–55% faster during recovery compared to mixing ventilation. Displacement ventilation also demonstrates greater energy-saving potential, with PMVs decreasing more rapidly at higher internal loads. However, it is more sensitive to supply air temperature variations, leading to spikes in local draft risk and vertical temperature differences. These findings highlight the critical role of ventilation strategies in shaping local discomfort, particularly during transition periods in demand response programs.