OBJECTIVES This study examines the association between psychological morbidity, social support, and demographic and clinical variables in adult children of cancer patients undergoing chemotherapy. Special attention was given to the variable level of parental dependency. The main predictors of caregiving burden were tested, as well as the mediating role of social support in the relationship between psychological morbidity and burden. METHODS A total of 214 adult children caregivers of parents with cancer were recruited in Northern Portugal central hospitals. Caregivers completed Portuguese versions of the Depression Anxiety and Stress Scales, Impact of Event Scale-Revised, Satisfaction with Social Support Scale, and Burden Assessment Scale. RESULTS Significant associations among psychological, demographic, and clinical variables were found. Adult children with a greater perception of parent's dependency showed more distress, higher posttraumatic stress disorder (PTSD) symptoms, greater caregiving burden, and less satisfaction with social support. Hierarchical regression analyses revealed the main predictors of caregiver burden to be as follows: being a woman, caregiving duration, having a dependent parent, more distress and PTSD symptoms, and poorer social support. Social support was found to be a partial mediator in the relationship between psychological morbidity and caregiver burden. CONCLUSIONS Results underscore the importance of perceived parental dependency in offspring's caregivers. Findings support the multidimensional issues associated to burden in this specific population, stressing satisfaction with social support as an important mediator between distress/PTSD and burden. Implications for further research as well as limitations of the present study are discussed. Psychosocial interventions should focus on caregivers' social resources to facilitate psychological well-being.