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Research has shown that pain and sleep disturbance often co-occur and influence each other over time in children and adolescents with chronic pain. Longitudinal studies examining the underlying mechanisms of this association are scarce and have focused primarily on the role of internalizing mental health symptoms and mood. This longitudinal study aimed to determine whether fatigue underlies the co-occurrence and mutual maintenance of sleep disturbance and pain over time in children and adolescents with chronic pain. Participants were 355 school-aged children and adolescents (mean age = 11.63 year old; 67% female) with chronic pain. The participants provided sociodemographic information and responded a survey that included measures of pain (duration, intensity, interference), sleep disturbance, and fatigue at first assessment and 12 months later. Partially latent, cross-lagged, panel, structural equation models revealed that sleep disturbance, pain intensity, and pain interference co-occurred at both time points. Higher levels of sleep disturbance, pain intensity, and pain interference at first assessment predicted higher levels of sleep disturbance, pain intensity, and pain interference at follow-up, respectively. Higher levels of pain interference at first assessment predicted higher levels of sleep disturbance at follow-up while controlling for initial levels of sleep disturbance. Furthermore, fatigue was found to mediate the association between first assessment and follow-up sleep disturbance, the association between first assessment and follow-up pain interference, and the association between first assessment pain interference and follow-up sleep disturbance. The findings highlight the need to assess and address fatigue in children and adolescents with chronic pain and sleep disturbance.