Background and objective: Exercise capacity is associated with health-related quality of life and symptom control in severe asthma. Thus, interventions targeting exercise capacity are likely to be beneficial. However, clinical and biological factors impacting exercise capacity in severe asthma are sparsely investigated. We aimed to describe the association of selected clinical and biological factors with 6-min walk distance (6MWD) in adults with severe asthma and investigate the impact of sex on these outcomes. Methods: A cross-sectional study in adults with severe asthma was conducted. Exercise capacity was measured by 6-min walk test, and association between 6MWD and predictors were evaluated using multiple linear regression. Results: A total of 137 patients (females, 85; median age, 59 years) were recruited. Overall, asthma control (−15.2 m, 95% CI −22.6 to −7.7; p = 0.0001) and BMI (−3.2 m, 95% CI −5.1 to −1.3; p = 0.001) were significantly associated with exercise capacity (adjusted variance, adj. R² = 0.425). In females, 5-item Asthma Control Questionnaire (ACQ-5; p = 0.005) and BMI (p < 0.001) were significantly associated with 6MWD (adj. R² = 0.423). In males, a 0.5-point increase in ACQ-5 was associated with a decrease in 6MWD by 10.2 m (95% CI −22.8 to 2.4; p = 0.11), but no clinical nor biological factors reached statistical significance (adj. R² = 0.393). Conclusion: Asthma symptoms and BMI were associated with exercise capacity in the overall population. Optimizing these factors may enhance the ability of patients to improve their exercise capacity and gain the associated positive health outcomes, but further studies are warranted.