Background and purposeTo estimate health‐related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)].MethodsWe performed a cross‐sectional observational study on patients with CCMs admitted to our department from 1 November 2017 to 10 January 2020 using standardized interviews [short‐form‐36 questionnaire, hospital anxiety and depression score (HADS‐A/D), CCM perception questionnaire]. Included criteria were diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. Health‐related quality of life (HRQOL) data were analyzed and compared to the German normal population. Uni‐ and multivariate analyses were carried out to identify variables with impact on outcome.ResultsTwo hundred nineteen (93%) of 229 eligible patients were included. Mean age was 46.3 ± 14.7 (18–86) years; 136 (62%) were female. Ninety‐eight (45%) patients presented with symptomatic hemorrhage (SH), and 17 (8%) with repetitive SH. Ninety‐two (42%) patients were asymptomatic. Thirty‐seven patients (17%) suffered from cavernoma‐related epilepsy. Twenty‐eight patients (13%) suffered from familial CCMs. Patients showed significantly decreased component scores and subdomain scores compared to the normal population, with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS‐A was significantly increased. HADS‐A/D strongly correlated with mental component score and individual perception of the CCM.ConclusionsPatients with the diagnosis of a CCM showed decreased HRQOL compared to the normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmarks in evaluation of different (future) management strategies.