Rationale: Severe asthma accounts for 3-10% of the total population of patients with asthma. Comorbid conditions are common in patients with asthma and can complicate asthma management in multiple ways. Data are scarce on the prevalence and patterns of comorbidities in the severe asthma subpopulation. Methods: The International Severe Asthma Registry (ISAR, http://isaregistries.org) contains comorbidity history data for 10,923 patients enrolled across 22 countries from 2000 through 2021 (database version: 13 October 2021). We assessed the prevalence of 33 comorbid conditions (11 potentially T2-related, 15 potentially related to long-term use of oral corticosteroids (OCS), and 7 potentially mimicking/exacerbating asthma) among countries reporting them. For comorbidities reported in at least 10% of patients overall, we compared the prevalence estimates by sex. Results: Overall, 91% of patients had at least 1 comorbidity reported. Potentially T2-related comorbidities, potential OCSrelated comorbidities, and comorbidities that may mimic or exacerbate asthma were reported in 69%, 63%, and 44% of patients, respectively. The prevalence estimates of individual comorbidities are shown in the Table. Nasal polyposis and sleep apnea were more prevalent in men than in women (22% vs. 17% and 24% vs. 20%, respectively); whereas the prevalence of obesity and dysfunctional breathing was lower in men than in women (39% vs. 46% and 7.0% vs. 13%, respectively) (p<0.0001). Conclusions: Comorbidity is highly prevalent in patients with severe asthma. More studies are warranted to assess their association with asthma-related outcomes, and to investigate the impact of T2-related comorbidities on patient response to biologic therapies.