Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index, BMI>25 kg/m2) for reasons that are not fully elucidated. Objectives: To determine the key physiological traits (upper-airway anatomy/collapsibility, upper-airway muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals. Methods: We compared key physiological traits in 18 overweight/obese non-apneics (apnea-hypopnea index, AHI<15 events/hr) to 25 overweight/obese matched OSA patients (AHI≥15 events/hr), and 11 normal-weight non-apneic controls. Traits were measured by repeatedly lowering continuous positive airway pressure to sub-therapeutic levels for 3 min during non-REM sleep. Measurements and Main Results: Overweight/obese non-apneics exhibited a less collapsible airway than overweight/obese apneics (Pcrit: -3.7±1.9 vs. 0.6±1.2 cmH2O, P=0.003; mean±95%CI.), but a more collapsible airway relative to normal-weight controls (-8.8±3.1 cmH2O, P<0.001). Notably, overweight/obese non-apneics exhibited a 3-fold greater upper-airway muscle responsiveness than both overweight/obese apneics (Δgenioglossus EMG/Δepiglottic pressure: -0.49[-0.22 to -0.79] vs. -0.15[-0.09 to -0.22] %/cmH2O, P=0.008; mean[95%CI]) and normal-weight controls (-0.16[-0.04 to -0.30] %/cmH2O; P=0.02). Loop gain was elevated (more-negative) in both overweight/obese groups vs. normal-weight controls (p=0.02). Model-based analysis demonstrated that overweight/obese non-apneics rely on both more favorable anatomy/collapsibility and enhanced upper-airway dilator muscle responses to avoid OSA. Conclusions: Overweight/obese non-apneics have a moderately-compromised upper-airway structure that is mitigated by highly-responsive upper-airway dilator muscles to avoid OSA. Elucidating the mechanisms underlying enhanced muscle responses in this population may provide clues for novel OSA interventions.