This study assessed the impact on health-related quality of life (HRQL) and the perceived burden of informal caregivers of individuals with Alzheimer’s disease (AD) on the Canary Islands (Spain). We utilized a multicenter, cross-sectional design, based on questionnaire responses of 237 informal caregivers of AD patients. Patients were classified according to the degree of severity utilizing the Clinical Dementia Rating Scale. Sociodemographic, HRQL (EQ-5D) and functional dependency data were gathered together with the degree of caregiver burden. Caregivers had a higher frequency of problems than did the general population for every EQ-5D dimension. Caregivers’ HRQL was inversely associated with the subject dependency level and caregiver age. HRQL was higher for more educated caregivers. Variables with a negative and/or significant effect on caregivers’ HRQL were high feelings of burden, more committed time to care, and older age. The caregiver burden quantified by the Zarit scale showed 83.3% of caregivers with a high level of burden.