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Intersectionality analysis is the study of overlapping or intersecting social identities. Intersecting social identities may have an impact on the perception of burden by family caregivers of older persons with multiple chronic conditions (MCC). The purpose of this study was to explore the interaction of social factors on the burden of caring for older adults with MCC. A total of 194 caregivers of older adults with MCC were recruited from Alberta and Ontario. Survey data were collected at two time points, six months apart. Additive and multiplicative models were analysed using a generalised linear model to determine the level of caregiver burden. Medium-high social interference (impact on social life) was associated with higher burden when adjusted for age, gender, education, and employment status. The overall results of the five-way interaction suggest that males in general had lower burden scores than females. Irrespective of their education and employment status, females had generally higher burden scores. These results add to the current body of literature, suggesting areas for further research to fill knowledge gaps, and promoting ideas for evidence-guided public health interventions that focus on caregivers.