This study aimed to determine whether self-efficacy beliefs mediated the relation between pain-related fear and pain, and between pain-related fear and disability in CLBP patients who exhibited high pain-related fear. In a cross-sectional design, 102 chronic low back pain (CLBP) patients completed measures for pain, disability, self-efficacy and pain-related fear (fear of movement and catastrophizing). Multistep regression analyses were performed to determine whether self-efficacy mediated the relation between pain-related fear and outcome (pain and/or disability). Self-efficacy was found to mediate the relation between pain-related fear and pain intensity, and between pain-related fear and disability. Therefore, this study suggests that when self-efficacy is high, elevated pain-related fear might not lead to greater pain and disability. However, in instances where self-efficacy is low, elevated pain-related fear is likely to lead to greater pain and disability. In view of these findings, we conclude that it is imperative to assess both pain-related fear and self-efficacy when treating CLBP patients with high pain-related fear.