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To explore the mediating effect of loneliness on the relationship between pain interference and depressive symptoms and to determine whether this mechanism is contingent on employment status.Cross-sectional study.A total of 876 adult caregivers of adolescents living in extremely impoverished conditions.Mediation and moderated mediation analyses using standard path-analytic approaches.The mean age of the sample was 39.0 (SD = 12.8) years and 80.7% (n = 707) identified as female. Almost half (48.9%, n = 425) of the participants did not report any pain, while 32.5% (n = 285) reported non-disabling pain, and 19.0% (n = 166) reported disabling pain. The mean depressive symptoms score was 16.20 (SD = 10.6), and the mean loneliness score was 40.09 (SD = 10.5). Loneliness mediated the effect of both non-disabling and disabling pain on depressive symptoms. However, the indirect effect of pain interference on depressive symptoms through loneliness was more pronounced among participants reporting disabling pain (coefficient, 2.11; Boot 95% confidence interval (CI) (1.25–3.01)) than non-disabling pain (coefficient, 0.99; Boot 95% CI (0.25–1.76)). Moderated mediation results showed that the indirect effect of pain interference on depressive symptoms, via loneliness varied in magnitude as a function of employment status among participants reporting disabling pain but not those reporting non-disabling pain.Loneliness provides an important link in the relationship between depressive symptoms and pain interference. Furthermore, employment status is an important factor to consider, especially among individuals reporting disabling pain with comorbid depressive symptoms.