Objective To evaluate the predictive performance of neuro-mechanical coupling (NMC) and neuro-ventilatory coupling (NVC) in the weaning outcome in patients with chronic obstructive pulmonary disease (COPD). Methods Sixteen patients were enrolled when the criteria for their first spontaneous breathing trial (SBT) was met. A 30-minute SBT was attempted, with the measurement of electrical activity of the diaphragm (Edi) , NMC, NVC, NVC ×NMC, index of rapid shallow breathing (f/Vt) , airway occlusion pressure (P0.1) and f/Vt ×P0.1 at 0, 5 and 30 min. The receiver operating characteristic (ROC) curve was calculated to evaluate the predictive performance of each index. Results Successful weaning(S group) was observed in 6 patients while weaning failure(F group) in 10 patients. (1)The predictive capacity of Edi: at 30 min of SBT, Edi showed higher values in the F group (P ＜ 0. 05), the area under the ROC curves(AUC) was 0. 817(P ＜0. 05). (2) The predictive capacity of NVC and NMC:at 5, 30 min of SBT, NVC and NMC showed higher values in the S group (P ＜0. 05); at 30 min of SBT NVC presented the largest AUC than any other time of SBT (0. 822, P ＜ 0. 05), while the AUC of NMC was 0. 800 (P ＞ 0. 05). (3) The predictive capacity of NVC × NMC: at 30 min of SBT, the AUC of NVC × NMC was larger than NVC (0. 864, P ＜ 0. 05) , showing greater sensitivity (100. 0%) and specificity (83. 3%) .(4) The predictive capacity of f/Vt and P0.1: f/Vt and f/Vt × P0.1 presented poor predictive performance in the failed patients. Conclusions Edi, NVC and NVC × NMC were good predictor for the weaning outcome in patients with COPD.