Informal caregivers are the core of long-term care for older and disabled people. Although previous research has studied factors that influence caregivers’ burden, little is known about the different care domains and why they influence the caregivers’ perceived burden. Drawing on a large-scale German survey, the current study makes a first attempt to address this research gap. The study used cross-sectional data on 1.429 informal caregivers. Germany is characterized by comprehensive but fragmented health and social protection systems oriented toward supporting informal care at home. Structural equation modeling (SmartPLS 3) was used to estimate the effects of five care domains on three burden dimensions and, ultimately, on the overall burden. Our results indicate that support in organizational matters had the highest impact on the overall perceived burden. The findings reveal that German caregivers particularly struggle with bureaucracy, i.e. an area that can directly be influenced by policymakers.