Objective To investigate the relation between serum leptin/tumor necrosis factor-α (TNF-α)and malnutrition in patients with chronic obstructive pulmonary disease (COPD) and stable chronic cor pulmonale (CCP) at high altitude. Methods Totally 162 COPD and CCP patients and 40 normal controls (group C) were studied. COPD and CCP patients were divided into malnutrition group (group A, n = 104) and normal nutrition group (group B, n =58) according to the nutritional parameters. Levels of serum leptin and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Results Body mass index (BMI), percentage of normal body weight (NW%), triceps skinfold thickness (TSF), mid-upper arm circumference (MAC), serum albumin (ALB) ingroupA[(17.4±1.8) kg/m2, (82.3±4.3)%, (7.0±2.6) mm, (17.8±2.8) cm, (30.3±3.9)g/L, respectively] were significantly lower than those in group B and group C [(21.8 ± 2.0) kg/m2,(98.6±5.5)%, (9.3±2.6) mm, (21.5±2.9) cm, (36.2±3.8) g/L, and (23.1±2.3) kg/m2,(102.2±5.2)%, (9.7±3.8) mm, (22.1±2.8) cm, (36.8±3.9) g/L, respectively; all P＜0. 01].The levels of serum leptin and TNF-α in group A [(9.5 ±1. 8) ng/ml and (17.3 ±2. 2) ng/ml, respectively]were significantly higher than those in group A and group C [(7.3 ± 2. 0) ng/ml, (13.5 ± 2. 3) ng/ml; and (6. 7 ±2. 3) ng/ml, (12. 8 ±2. 1) ng/ml, respectively; all P ＜0.01). However, they were not significantly different between group A and group B (all P ＞ 0. 05). The level of leptin was negatively correlated with BMI (r=-0.745, P=0. 0005), NW% (r= -0.887, P=0. 0005), TSF (r= -0.725, P=0. 0005), MAC (r= -0. 761, P=0. 0005), serum albumin (r= -0. 558, P=0. 0005) in group A, and was positively correlated with TNF-α (r = 0. 527, P = 0. 0005). Conclusion Serum leptin and TNF-α correlate with malnutrition in patients with COPD and CCP at high altitude.