This study examined the relationship between the VO2 response, particularly the slow component (SC), muscle metabolite changes and performance during very-heavy exhaustive exercise. Sixteen active females performed a graded exercise test to determine V*O2 peak and the lactate threshold followed 48 h later by a constant-load cycle test to exhaustion (ET) at 85% V*O2 peak intensity. Muscle biopsies and capillary blood samples were obtained before and after the ET to determine changes in muscle ATP, pH, lactate and phosphocreatine and also plasma pH and lactate. Breath-by-breath data from the ET were smoothed using 5-s averages and fit to a three-component exponential model. The mean time to exhaustion (texh) during the ET was 16.8 (6.4) min. Results showed no correlation between the SC and texh or any muscle metabolite changes (p>0.05). Significant correlations (p<0.05) were evident between texh and tau; τ0 (r = -0.54), τ1 (r = -0.65), change in () pHb (r= -0.60), [La-]b (r= -0.58) and [La-]b post (r = -0.64). Significant correlations (p<0.05) were also evident between τ1 and [La-]b post (r= 0.54). Furthermore, a negative value resulted when the accumulated oxygen deficit was calculated for the entire duration of the ET. Results showed no association between the amplitude of the SC and text or to changes in muscle/blood metabolites, suggesting that the SC is not a determinant of high-intensity exercise tolerance. Furthermore, it is possible that a reduced perturbation of anaerobic energy sources, as a result of a faster τ1, may have contributed to a longer texh.