Epidemiological and cross-sectional studies have shown that post-traumatic stress disorder symptoms (PTSS) are common and impairing in youth with chronic pain. Yet, the co-occurrence of PTSS and pediatric chronic pain has not been examined longitudinally, which has limited understanding of theoretically proposed mechanisms (eg, sleep disturbance) underlying the PTSS-pain relationship over time. This longitudinal study aimed to fill this gap. Participants included 138 youth (Mage = 14.29, 75% girls) referred to a tertiary-level outpatient chronic pain program and one of their parents. At baseline, youth reported their pain intensity and interference, PTSS, and subjective sleep disturbances (ie, sleep quality and insomnia). Youth and parents completed semistructured diagnostic interviews to determine the child's post-traumatic stress disorder diagnostic status, and youth completed an objective assessment of sleep patterns for 7 days using actigraphy. At 3-month follow-up, youth once again completed the diagnostic interview and reported their pain intensity, pain interference, and PTSS. Partially latent cross-lagged structural equation panel models revealed that, controlling for pain intensity, pain interference and PTSS co-occurred at baseline, but not at follow-up (while controlling for baseline levels). Higher levels of baseline PTSS were predictive of increases in pain interference at follow-up. Furthermore, subjective sleep disturbances mediated the relationship between baseline PTSS and follow-up pain interference. These findings lend support to conceptual models of PTSS-pain co-occurrence and highlight a critical need to assess and address trauma and sleep disturbances in youth with chronic pain.