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The present study: (a) examined the extent of caregiver burden and psychological wellbeing and (b) tested whether social connectedness moderated the association between caregiver burden and psychological symptoms in caregivers of people with cancer. The cross-sectional survey study included 189 cancer caregivers (mean age = 36.19 years, standard deviation = 11.78; 80.4% female). Data were collected on caregiver burden, social connectedness, and depression and anxiety. Moderation analysis was conducted to examine the effect of social connectedness on the relationship between caregiver burden and depression and anxiety. Caregiver burden was positively associated with depression and anxiety symptoms. Controlling for significant demographic and caregiver characteristics, the moderation model showed as perceived social connectedness increased, the relationship between caregiver burden and depression decreased (β = −0.007, se = 0.004, 95% CI: −0.014, 0.000, p = 0.05). By contrast, social connectedness did not moderate the association between caregiver burden and anxiety. Findings have implications for the management of depression in cancer caregivers. Social connectedness appears to provide a protective buffer from the negative impacts of caregiving, providing increased psychological resources to manage the burden associated with caregiving, resulting in lower depression. Research on strategies to improve caregiver wellbeing through enhancing engagement with social networks in ways that improve perceived sense of connectedness with others is warranted. [ABSTRACT FROM AUTHOR]