The downward slope during the near-infrared spectroscopy (NIRS)-vascular occlusion test (NIRS-VOT) is purported as a simplified estimate of metabolism. Whether or not the NIRS-VOT exhibits sex- or limb-specificity or may be acutely altered remains to be elucidated. Thus, we investigated if there is limb- or sex specificity in tissue desaturation rates (DeO(2)) during a NIRS-VOT, and if acute dietary capsaicin may alter this estimate of muscle metabolism. Young healthy men (n = 25, 21 +/- 4 years) and women (n = 20, 20 +/- 1 years) ingested either placebo or capsaicin, in a counterbalanced, single-blind, crossover design after which a simplified NIRS-VOT was conducted to determine the DeO(2) (%/s), as an estimate of oxidative muscle metabolism, in both the forearm (flexors) and thigh (vastus lateralis). There was a significant limb effect with the quadriceps having a greater DeO(2) than the forearm (-2.31 +/- 1.34 vs. -1.78 +/- 1.22%/s, p = 0.007, eta(2)(p) = 0.19). There was a significant effect of sex on DeO(2) (p = 0.005, eta(2)(p) = 0.203) with men exhibiting a lesser DeO(2) than women (-1.73 +/- 1.03 vs. -2.36 +/- 1.32%/s, respectively). This manifested in significant interactions of limb*capsaicin (p = 0.001, eta(2)(p) = 0.26) as well as limb*capsaicin*sex on DeO(2) (p = 0.013, eta(2)(p) = 0.16) being observed. Capsaicin does not clearly alter O-2-dependent muscle metabolism, but there was apparent limb and sex specificity, interacting with capsaicin in this NIRS-derived assessment.