Patients with chronic illnesses, such as chronic obstructive pulmonary disease (COPD), report an increase in the perception of fatigue in the clinical setting. Subjective fatigue associated with physiological factors has not been reported. The purpose of this study was to determine the relationship between subjective fatigue and pulmonary function, respiratory and peripheral muscle force and exercise capacity in patients with COPD. Nineteen patients with COPD participated in the study [mean (SD) FEV1 38% (17%) predicted]. Fatigue was measured with the Multidimensional Fatigue Inventory 20 (MFI-20) that includes the following subscale dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. The following physical variables were measured: forced expiratory volume in 1 s (FEV1), vital capacity (VC), maximal inspiratory peak pressure (PImax), symptom-limited bicycle exercise capacity (maximum workload) and maximal voluntary isometric muscle force of both left and right quadriceps (Qu), hamstrings (Ha), biceps (Bi) and triceps (Tr). The MFI-20 fatigue dimensions, reduced activity and reduced Motivation, are significantly correlated with FEV1 (% predicted) (r = -0.62, r = -0.55 respectively). No significant correlation was found between the dimensions of fatigue and maximum workload. In contrast the fatigue dimension, physical fatigue, shows significant correlations with seven of eight muscle forces measured (Qu left r = -0.49, right r = -0.54; Ha left r = -0.49, right r-0.38; Tr left r = -0.61, right r = -0.45; Bi left r = -0.46, right r = -0.48). Data from this study show that activity and physical dimensions of subjective fatigue are related to pulmonary function and skeletal muscle force in COPD patients. Interventions to improve skeletal muscle force might improve subjective fatigue in patients with COPD.