Abstract The effectiveness of the fatigue behavior of the large-scale reinforced concrete (RC) beams strengthened with side near surface mounted (SNSM) carbon fiber-reinforced plastics (CFRP) was assessed. Six RC beams (three static beams and three fatigue beams, strengthened with SNSM non-prestressed and prestressed CFRP strips) were tested to investigate the effects of the different loading and strengthening methods on the flexural fatigue performance of the beams. In order to simulate the existence of a certain degree of initial damage when the service beams were strengthened, the fatigue test beams were strengthened after they had been subjected to 2 million fatigue cycle loading, and then continued to be subjected to 500,000 fatigue cycle loading. The results showed that the flexural capacity and ductility of static strengthened beams were obviously higher than that of the un-strengthened beam, and the residual flexural capacity of the fatigue test beams was significantly lower than those of the static test beams. In terms of fatigue resistance, the prestressed CFRP strengthened beam was superior to the non-prestressed CFRP one; the tests beams were better after being strengthened than before. The damage of the strength of the concrete and steel bars was mainly accumulated at the initial stage of fatigue cycle loading, where the stiffness of the test beams decreased rapidly. The steel bar strain, concrete strain and mid-span deflection of strengthened beams after 2.5 million loading of fatigue cycles were basically the same as those of 2 million one, which indicated that the fatigue flexural behavior of the strengthened beams was enhanced significantly. Finally, the predicted models of static mid-span deflection and fatigue residual flexural capacity for the SNSM strengthening beams were derived and validated.