Aims: This study investigates a possible added subjective burden among informal caregivers to care recipients with a mental illness or a combination of mental and somatic illnesses compared with caregivers to care recipients with a somatic illness. The study also investigates the subjective caregiver burden by caregivers’ characteristics and objective burden. Methods: The association between subjective caregiver burden and socio-demographic factors, objective burden, and health-related quality of life was analyzed in a population of 865 Dutch informal caregivers, using multiple linear regression analysis. Results: Controlling for other factors in the analysis, we found that caring for a recipient with mental illness or a combination of mental and somatic illness was associated with an extra subjective caregiver burden (measured by Caregiver Strain Index). Objective burden, in terms of more than 50 hours of care provision per week, less than three years of caregiving, or living together with the care recipients was associated with higher subjective caregiver burden. Other factors associated with higher subjective caregiver burden were being partners or a child of care recipient, having a paid job, a low health-related quality of life (EQ-5D), or having an illness. Conclusions: This study suggests that caregivers to care recipients with a mental and especially a combination of mental and somatic illnesses have a higher subjective caregiver burden compared with caregivers to care recipients with a somatic illness. Because the study is not representative of all caregivers, more research focusing on identifying and contacting informal caregivers is needed to confirm the result.