Purpose: Our aim was to investigate associations between the subjective burden of care and health-related quality of life (both physical and mental) within colorectal cancer patient carers in Ireland, with supplementary analysis of carer objective factors. Methods: Two hundred twenty-eight colorectal cancer informal carers were sent a postal questionnaire between August 2010 and March 2011 which included the Caregiver Reaction Assessment (CRA) and the SF-12v2. Multiple regression analysis assessed whether five CRA domains (family support, finances, schedule, health and esteem) predicted carer mental or physical health. Between-group comparisons investigated differences in these domains across objective factors. Results: One hundred fifty-three carers (82 % female) completed the questionnaire (response rate = 68 %). Carers’ mean physical component summary (PCS) was 48.56 (SD = 10.38) and mean mental component summary (MCS) was 49.22 (SD = 9.7). Five CRA factors explained 30 % of variance in the PCS score and 28 % of variance in the MCS score. Health burden (β = −.76, p < .001) and schedule burden (β = .28, p = .01) were significant predictors of PCS. MCS was significantly predicated by financial burden (β = −.24, p = .01) and esteem (β = −.18, p = .03). Younger carers, spouses, those with a comorbid condition and those with no income change had significantly lower PCS. There were no statistically significant group differences for carer mental health. Conclusions: Our results demonstrate the need to recognise the distinctive aspects of the impact of caring (i.e., physical and mental) on carers and that different domains of subjective carer burden and objective factors impact differently on each of these. This has important implications for those delivering support to carers over the course of the survivorship continuum.