BACKGROUND: Inflammation plays a major role in the development of atherosclerosis. We wanted to investigate the effects of exercise on high-sensitivity (hs) C-reactive protein (CRP) in subjects who were suspected of having coronary artery disease (CAD). METHODS: Blood samples were obtained before, 5 minutes after, and 20 hours after an exercise test in 155 subjects who were suspected of CAD. Coronary anatomy was evaluated by computed tomography coronary angiography and/or coronary angiography. RESULTS: Median baseline hs-CRP was higher in subjects with ≥50% coronary artery lumen diameter stenosis (n=41), compared with non-CAD-subjects (n=114), 2.93 mg/L (interquartile range 1.03-5.06 mg/L) and 1.30 mg/L (interquartile range 0.76-2.74 mg/L), respectively, P=0.007. In multivariate analyses testing conventional risk factors, hs-CRP proved borderline significant, odds ratio =2.32, P=0.065. Adding baseline hs-CRP to the results of the exercise test did not improve the diagnostic evaluation. Baseline natural logarithm (Ln) hs-CRP was positively associated with body mass index and baseline Ln-transformed hs troponin T levels, and negatively associated with the daily life activity level. An increase in hs-CRP of 0.13 mg/L (interquartile range 0.05-0.24 mg/L) from baseline to 5 minutes after peak exercise was found (P<0.0001), but the increase was not associated with presence of CAD. From baseline to 20 hours after exercise, no increase in hs-CRP was found. CONCLUSION: In conclusion, hs-CRP was not independently associated with CAD. Hs-CRP increased immediately as a response to the exercise, and the increase was modest and not associated with CAD. The results indicate that exercise has potential to cause unwanted variations in hs-CRP and that exercise prior to hs-CRP measurements in subjects included in epidemiological studies, therefore, should be avoided.