Despite our knowledge of the risk factors for mortality associated with chronic obstructive pulmonary disease (COPD), the mortality rate for this condition continues to increase. This study aimed to investigate the predictive power of physiological variables on all-cause mortality in COPD patients compared to peak oxygen uptake (O2peak) and forced expired volume in one second (FEV1). We conducted a retrospective study of 182 COPD patients with complete lung function tests, cardiopulmonary exercise testing (CPET), and survival data. Cox regression analysis was used to estimate the hazard ratios for all-cause mortality. The median follow-up period was 6.8 (IQR 3.9-9.2) years. Out of the 182 patients in our study, sixty-two (34.1%) succumbed to various causes. Of these, 27.4% (n = 17) experienced acute exacerbations, 24.2% (n = 15) had advanced cancer, and 12.9% (n = 8) had cardiovascular disease as the primary cause of death. Another 25.8% (n = 16) passed away due to other underlying conditions, while 6.5% (n = 4) had an unknown cause of death. One patient's demise was attributed to a benign tumor, and another's to a connective tissue disease. The ratio of tidal volume to total lung capacity (VTpeak/TLC) and the ratio of minute ventilation and O2 at nadir (E/O2nadir) (AUR 0.83, 95% CI 0.76-0.91) were superior predictors of all-cause mortality compared to O2peak and FEV1%. A mortality prediction formula was derived using these variables. This study highlights the potential of VTpeak/TLC and E/O2nadir as predictive markers for COPD all-cause mortality in COPD. CPET is an effective tool for evaluating COPD mortality; however, the predictive equation requires further validation.