The present study investigates the association between the severity of coronary artery disease (CAD) and feelings of exhaustion. Vital exhaustion consists of three major components: lack of energy, increased irritability, and demoralization. Previous studies showed that exhaustion is of predictive value for first myocardial infarction (MI). However, these studies could not rule out that the state of exhaustion prior to MI was the result of underlying CAD. To examine this issue, severity of CAD and cardiac pump function were related to feelings of exhaustion in 307 patients who underwent coronary angiography. It was found that exhaustion, as assessed by means of the Maastricht Questionnaire (MQ), was not related to the severity of CAD (F = 1.17; p = 1.05). Furthermore, a poor left ventricular function did not relate to MQ scores (N = 138; F < 1; NS). On the other hand, clinical variables (duration of complaints, exercise performance, peripheral vascular disease, and dyspnea), use of medication (nitrates, beta-blocking agents, calcium antagonists, and diuretics), and demographic characteristics (gender and education) were associated with MQ scores. Multiple regression analysis showed that demographic variables (lower education, younger age, and female gender) were the predominant predictors of exhaustion. In addition, dyspnea, peripheral vascular disease, and the use of medication related significantly to exhaustion scores (R2 = 0.13; F = 4.8; p < 0.001). We conclude that neither the extent of CAD nor impaired cardiac pump function is related to feelings of exhaustion in patients referred for coronary angiography. Therefore, the previously reported association between exhaustion and future MI is not likely to be caused by underlying coronary disease.