AbstractObstructive sleep apnea (OSA) is a highly prevalent sleep disorder, which results in daytime symptoms, a reduced quality of life as well as long-term negative health consequences. OSA diagnosis and severity rating is typically based on the apnea-hypopnea index (AHI) retrieved from overnight poly(somno)graphy. However, polysomnography is costly, obtrusive and not suitable for long-term recordings. Here, we present a method for unobtrusive estimation of the AHI using ECG-based features to detect OSA-related events. Moreover, adding ECG-based sleep/wake scoring yields a fully automatic method for AHI-estimation. Importantly, our algorithm was developed and validated on a combination of clinical datasets, including datasets selectively including OSA-pathology but also a heterogeneous, “real-world” clinical sleep disordered population (262 participants in the validation set). The algorithm provides a good representation of the current gold standard AHI (0.72 correlation, estimation error of 0.56 ± 14.74 events/h), and can also be employed as a screening tool for a large range of OSA severities (ROC AUC ≥ 0.86, Cohen’s kappa ≥ 0.53 and precision ≥70%). The method compares favourably to other OSA monitoring strategies, showing the feasibility of cardiovascular-based surrogates for sleep monitoring to evolve into clinically usable tools.