Purpose <p>Caregiver burden and psychological distress have been found to have well established links in caretaker literature; however, the underlying mechanisms between them have been less frequently studied. This study aims to examine one such pathway between caregiver burden and psychological distress, through the mediating roles of rumination and hopelessness.</p> Method <p>A total of 143 parents of children with neurodevelopmental disorders in Pakistan were interviewed using the <i>Zarit Burden interview</i>,<i> short version Ruminative Responses Scale</i>,<i> State-Trait Hopelessness Scale</i> and <i>the Kessler Psychological Distress Scale</i>. Pearson Product Moment and Hayes Process Macro Model 6 was employed to analyze correlational and mediation effects.</p> Results <p>Results indicated significant associations between study variables and the mediation analysis results showed caregiver burden to have a significant direct effect on psychological distress. Rumination did not directly mediate the association between caregiver burden and psychological distress, however, rumination and hopelessness significantly mediated the association between caregiver burden and psychological distress experienced.</p> Conclusion <p>This study suggests significant associations between caregiver burden, rumination, hopelessness, and psychological distress and has important implications for future longitudinal research and interventions targeting distressed parents in Pakistan. Such findings may help clinicians consider rumination and state of hopelessness as risk factors while assessing psychological distress in the context of caregiving burden and may inform the design of preventive interventions targeting faulty cognitive patterns to manage ruminating and hopeless thoughts to potentially reduce psychological distress.</p>