Background. Reaction time is a reliable indicator of the velocity and efficiency of neuromuscular control and may be associated with fear-avoidance beliefs. However, the effect of exercise-induced muscle fatigue on reaction time in chronic low back pain (cLBP) and its relationship with fear-avoidance beliefs remains poorly understood. Objectives. This study aimed to reveal the relationship between fear-avoidance beliefs and reaction time changes before and after exercise-induced muscle fatigue in cLBP. Methods. Twenty-five patients with cLBP were tested by the Biering–Sorensen test (BST) to induce exhaustive muscle fatigue. Total reaction time (TRT), premotor time (PMT), and electromechanical delay (EMD) of dominated deltoid muscle were recorded by surface electromyography during the arm-raising task with visual cues before and after muscle fatigue. The mean difference (MD) of TRT (MDTRT), PMT (MDPMT), and EMD (MDEMD) was calculated from the changes before and after muscle fatigue. Fear-avoidance beliefs questionnaire (FABQ) was applied to evaluate fear-avoidance beliefs before muscle fatigue. In addition, the duration time of BST was recorded for each subject. Results. TRT and PMT of dominated deltoid muscle were prolonged after exercise-induced muscle fatigue (Z = 3.511, p<0.001; t = 3.431, p=0.001), while there was no statistical difference in EMD (Z = 1.029, p=0.304). Correlation analysis showed that both the MDTRT and MDPMT were positively correlated with FABQ (r = 0.418, p=0.042; r = 0.422, p=0.040). Conclusions. These findings suggested that we should pay attention to both muscle fatigue-induced reaction time delay in cLBP management and the possible psychological mechanism involved in it. Furthermore, this study implied that FABQ-based psychotherapy might serve as a potential approach for cLBP treatment by improving reaction time delay. This trial is registered with ChiCTR2300074348.