Abstract Body (Do not enter title and authors here): BACKGROUND: Anatomic burden of coronary artery disease (CAD) has been considered a consistent prognostic marker. Inflammation also increases the cardiovascular risk and plays a significant role in the evolution of atherosclerosis. The progression of CAD impacts the responses to exercise, reducing functional capacity. Despite this knowledge, the specific interplay between inflammation and atherosclerotic burden in influencing submaximal exercise capacity, particularly oxygen uptake (VO₂) kinetics, remains underexplored in CAD. This study aims to investigate how these factors correlate with VO₂ on-kinetics in the Six-minute Walk Test (6MWT) in patients with CAD. METHODS: Patients with obstructive CAD, confirmed by coronary angiography, underwent a 6MWT using a mobile telemetric cardiopulmonary monitoring to assess functional capacity and the VO₂ on-kinetics through the mean response time corrected by work (wMRT). Inflammatory markers were analyzed by dosage of high-sensitivity C-reactive protein, interferon-gama, tumor necrosis factor alpha and interleukins (IL), IL-6, IL-8 and IL-10. Coronary atherosclerotic burden was evaluated by the Grading Scale for Anatomic Burden of Disease from COURAGE Trial. Correlation analyses were performed according to the symmetric distribution of data, using Pearson’s (r) or Spearman’s rank correlation coefficients(r_s). RESULTS: A total of thirty-four patients aged between 60.3±8.0 years were enrolled, presenting body mass index of 26.0±3.7kg/cm², left ventricular ejection fraction of 0.50±0.14, walking distance of 443±66m, VO₂ at steady-state (VO_2SS) of 896±240ml/min and wMRT of 1.64x10^-3 ± 1.00x10^-3min²/ml. Although correlated with distance and VO_2SS (r=-0.472;p=0.002 and r=-0.434;p=0.015, respectively), atherosclerotic burden was not associated with wMRT (p=0.17). High-sensitivity C-reactive protein and IL-8 were negatively associated with both distance and VO_2SS (r_s=-0.428;p=0.001/ r_s=-0.543;p=0.001 and r_s=-0.438;p=0.014/ r_s=-0.407;p=0.019) and positively correlated with wMRT (r_s=0.412;p=0.022/ r_s=0.505;p=0.003). CONCLUSION: In contrast to anatomic burden, inflammatory markers were associated with both walking intensity and VO₂ kinetics. Therefore, inflammation may be more crucial to exercise response mechanisms than coronary stenosis, suggesting a paradigm shift in our understanding of clinical repercussions of obstructive CAD. Actions able to attenuate the inflammatory profile may improve exercise capacity and prognosis.