•Weber classification distinguished amongst differing clinical phenotypes in a cohort of patients with COPD.•Prediction equations developed became more accurate when applied to severe COPD patients.•Our data may be relevant as they bring important information to clinical practice through Weber class group stratification, which can be an important tool in determining clinical status and prognosis as well as guide clinical decision making. Weber classification stratifies cardiac patients based on peak oxygen consumption (V̇O2), the gold-standard measure of exercise capacity. To determine if Weber classification is a useful tool to discriminate clinical phenotypes in COPD patients and to evaluate if disease severity and other clinical measures can predict V̇O2peak. Three hundred and six COPD patients underwent cardiopulmonary exercise testing (CPX) and were divided according to Weber class: 1) Weber A (n = 34); 2) Weber B (n = 88); 3) Weber C (n = 138); and 4) Weber D (n = 46). Weber class D patients demonstrated a reduced V̇O2 peak, heart rate (HR), minute ventilation (V̇E), oxygen (O2) pulse, circulatory power (CP), oxygen uptake efficiency slope (OUES), oxygen saturation (SpO2%), delta (Δ)HR and ΔSpO2 when compared to Weber A and B (p<0.05). Moreover, Dyspnea and the V̇E/carbon dioxide production (V̇CO2) slope were higher in Weber D compared with Weber C and A (p<0.001). Hierarchical regression analysis demonstrated significant predictors of V̇O2peak (R2= 0.131; Adj R 2 = 1.25), including HR (β=0.5757; t = 5.7; P<0.001) and forced expiratory volume in one second (FEV1) (β=0.119; t = 2.16; P<0.03). Among the Weber C + D groups, predictors of V̇O2peak (R = 0.78; R2= 0.60; Adj R2 =0.59), dyspnea (β=0.076; t = 1.111; P<0.27) and maximal voluntary ventilation (MVV) (β=0.75; t = 1.14; P<0.00). Weber classification may be a useful tool to stratify cardiorespiratory fitness in COPD patients. Other clinical measures may be useful in predicting peak V̇O2 in mild-to-severe COPD, moreover different phenotypes may be important tool to improve physical capacity of chronic disease patients.