Previous investigators have demonstrated in patients with obstructive sleep apnea that weight reduction results in a decrease in apnea severity. Although the mechanism for this decrease is not clear, we hypothesize that decreases in upper airway collapsibility account for decreases in apnea severity with weight loss. To determine whether weight loss causes decreases in collapsibility, we measured the upper airway critical pressure (Pcrit) before and after a 17.4 ± 3.4% (mean ± SD) reduction in body mass index in 13 patients with obstructive sleep apnea. Thirteen weight-stable control subjects matched for age, body mass index, gender (all men), and non-REM disordered breathing rate (DBR) also were studied before and after usual care intervention. During non-REM sleep, maximal inspiratory airflow was measured by varying the level of nasal pressure and Pcrit was determined by the level of nasal pressure below which maximal inspiratory airflow ceased. In the weight loss group, a significant decrease in DBR from 83.3 ± 31.0 to 32.5 ± 35.9 episodes/h and in Pcrit from 3.1 ± 4.2 to −2.4 ± 4.4 cm H2O (p < 0.00001) was demonstrated. Moreover, decreases in Pcrit were associated with nearly complete elimination of apnea in each patient whose Pcrit fell below −4 cm H2O. In contrast, no significant change in DBR and a minimal reduction in Pcrit from 5.2 ± 2.3 to 4.2 ± 1.8 cm H2O (p = 0.031) was observed in the “usual care” group. We conclude that (1) weight loss is associated with decreases in upper airway collapsibility in obstructive sleep apnea, and that (2) the resolution of sleep apnea depends on the absolute level to which Pcrit falls.