Background: Investigation for the presence of asthma comorbidities is recommended by GINA as their presence can complicate asthma management. Objective: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. Methods: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. Thirty comorbidities were identified and categorized a priori as either (1) potentially T2-related, (2) potentially oral corticosteroid (OCS)-related or (3) mimicking/aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex. Results: Of 11,821 patients, 69%, 67%, and 55% had ≥1 potentially T2-related, potentially OCS-related, or mimicking/aggravating comorbidities, respectively; 57% had ≥3 comorbidities, and 33% had comorbidities in all three categories. Patients with allergic rhinitis (AR), nasal polyposis (NP), and chronic rhinosinusitis (CRS) experienced 1.12- (p=0.003), 1.16- (p<0.001) and 1.29-times (p<0.001) more exacerbations/year, respectively, than those without. Patients with NP and CRS were 40% and 46% more likely (p<0.001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with greater likelihood of LTOCS use (ORs: 1.23-2.77) and, except for dyslipidemia, with greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking/aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81) and all (except COPD) with increased likelihood of LTOCS use (ORs: 1.37-1.57). Greater number of comorbidities was associated with worse outcome. Conclusion: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes.