In a central heating, ventilation, and air conditioning (HVAC) system, the set-points for several local control loops have a significant influence on the overall energy performance of the system. Real-time optimization (RtOpt) of those set-points has therefore been widely studied. However, due to the nonlinear dynamics of the HVAC system as well as the constraints associated with the system operation, real-time optimization always suffers from a heavy on-line computational load when those set-points are optimized simultaneously. To overcome this problem, multiplexed real-time optimization (MRtOpt) has been developed, which optimizes only one set-point at a time but with a faster optimization frequency. Because frequently resetting the set-points introduces artificial disturbances into the local control loops and may deteriorate the system stability, this paper presents a study to enhance the system stability of the multiplexed real-time optimization by integrating a degree of freedom (DOF) based set point reset to renew the set-points instead of the conventional step-change set-point reset. The control performance of the integrated strategy was investigated using case studies. The results showed that around 10% of the energy saving was achieved by the proposed method compared with a method without real-time optimization. When compared with the conventional real-time optimization method, the proposed method resulted in around 70% computational load reduction, and over 26% reduction in the tracking errors of the local control loops. (C) 2016 Elsevier Ltd. All rights reserved.