Abstract The increasing use of Fiber Reinforced Polymer (FRP) for strengthening applications initiates the need to study the behavior of the strengthened members when subjected to fatigue loading. A general Fatigue Prediction Model (FPM) of Reinforced Concrete (RC) beams strengthened using prestressed FRP reinforcement was developed and presented in this paper. The damage effect was quantified into certain variables which can be determined analytically and/or experimentally. The developed model is applicable for any type of FRP strengthening. It accounts for the degradation in the concrete stress–strain relationship and the degradation of the epoxy-concrete and the steel–concrete bonds. The model was calibrated with experimental test results of RC beams strengthened using prestressed Near-Surface-Mounted (NSM) carbon FRP strips followed by performing a parametric study concerning the different model variables. It was found that the developed model accounts properly for the non-linearity in the strain variation across the depth of the RC strengthened beams as well as the effect of changing the prestress level when subjected to fatigue loading.