Introduction/purpose: This study tested the hypothesis that the respiratory compensation point (RCP) and breakpoint in deoxygenated [heme] (deoxy[heme]BP, assessed via near-infrared spectroscopy (NIRS)) during ramp incremental exercise would occur at the same metabolic rate in the upright (U) and supine (S) body positions. Methods: Eleven healthy men completed ramp incremental exercise tests in U and S. Gas exchange was measured breath-by-breath and time-resolved-NIRS was used to measure deoxy[heme] in the vastus lateralis (VL) and rectus femoris (RF). Results: RCP (S: 2.56 ± 0.39, U: 2.86 ± 0.40 L.min-1, P = 0.02) differed from deoxy[heme]BP in the VL in U (3.10 ± 0.44 L.min-1, P = 0.002), but was not different in S in the VL (2.70 ± 0.50 L.min-1, P = 0.15). RCP was not different from the deoxy[heme]BP in the RF for either position (S: 2.34 ± 0.48 L.min-1, U: 2.76 ± 0.53 L.min-1, P > 0.05). However, the deoxy[heme]BP differed between muscles in both positions (P < 0.05), and changes in deoxy[heme]BP did not relate to delta RCP between positions (VL: r = 0.55, P = 0.080, RF: r = 0.26, P = 0.44). The deoxy[heme]BP was consistently preceded by a breakpoint in total[heme], and was, in turn, itself preceded by a breakpoint in muscle surface electromyography (EMG). Conclusions: RCP and the deoxy[heme]BP can be dissociated across muscles and different body positions and, therefore, do not represent the same underlying physiological phenomenon. The deoxy[heme]BP may, however, be mechanistically related to breakpoints in total[heme] and muscle activity.