Background: Carers provide both practical and emotional support and often play an important role in coordination of care for recipients. The demands of caring may lead to increased levels of stress for the carer, which can affect mental health and quality of life. This study examined the relationship between being a carer and psychological distress (assessed using the Kessler Psychological Distress Scale [K10]), and explored the moderating effect of social support in that relationship using a large sample. Methods: The study used data from the 45 and Up study, a large cohort study of individuals aged 45 years and over in New South Wales, Australia, and applied multiple regression methods and moderation analysis. The sample for the current study comprised 267,041 participants drawn from the baseline dataset, with valid data on the primary outcome (carer status). Results: The mean age of participants was 62.73 (±11.18) years, and 4.23% and 7.13% were identified as full-time and part-time carers, respectively. Compared to non-carers, full-time carers had K10 scores that were on average, higher by 1.87, while part-time carers' K10 scores were on average higher by 1.60 points. A perception of social support reduced the strength of the relationship between carer status and psychological distress by 40% for fulltime carers and 60% for part-time carers. Conclusions: The findings have important implications, for both prevention and treatment of psychological problems among carers. In terms of prevention, they suggest that public health campaigns focused on increasing awareness regarding the psychological burden faced by carers would be useful. In terms of intervention, potential treatments that focus on improving social support networks may be helpful. The results are particularly important in the current context of an ageing population in Australian and other developed countries, where caregiving is likely to play an increasing role in the care and support services.