Pain-related guilt is a common yet unexplored psychological factor in low back pain (LBP). It has recently been linked to greater depression, anxiety and disability in LBP, hence an understanding of how it can be managed in the presence of pain and disability is necessary. Since acceptance of pain has been shown to be associated with improved outcomes in chronic pain, we examined whether it might also help reduce guilt in people with LBP. To this end, a series of mediation analyses were conducted on data from 287 patients with chronic LBP, in which acceptance of pain was tested as a mediator of the relationship between pain/disability and guilt. Results showed that acceptance of pain reduced the impact of pain/disability on pain-related guilt in all mediation analyses. Pain-related guilt might be a potential target for acceptance based interventions, thus this relationship should be further tested using longitudinal designs.