Human cardiovascular control during exercise is regulated by the arterial baroreflex and muscle afferent feedback (Raven et al., 2006). Muscle metaboreflex activation does not affect carotid-cardiac (CBR-HR) or carotid-vasomotor (CBR-MAP) baroreflex maximal gain in humans (Drew et al., 2008). Low-dose aspirin inhibits production of the metabolite thromboxane (TX) A2. However, it is unknown if inhibiting TX A2 affects CBR-HR and CBR-MAP maximal gain during muscle metaboreflex activation. Therefore, we examined the effect of inhibiting TX A2 production via low-dose aspirin on CBR-HR and CBR-MAP maximal gain during muscle metaboreflex activation in humans. 9 subjects performed two trials twice, each after 7-days of placebo or low-dose aspirin. A 5min baseline (rest) was followed by either 1.5min of continued rest (0% maximal voluntary contraction (MVC)) or isometric right calf exercise at 70% MVC, then 3.5min of circulatory occlusion (post-exercise circulatory occlusion (PECO) if exercise was performed). Paired-samples t-test and repeated measures ANOVA were used for statistical analysis. Aspirin reduced baseline TX B2 by ~90% (p<0.05). Maximal gain during rest was similar in all trials for CBR-HR and CBR-MAP (p>0.05) (Table 1). Both CBR-HR and CBR-MAP maximal gain during circulatory occlusion were similar in all trials, including during PECO (p>0.05) (Table 1). These results suggest that TX A2 inhibition via low-dose aspirin does not affect CBR-HR or CBR-MAP maximal gain during muscle metaboreflex activation in humans. This contrasts with previous preliminary findings showing that low-dose aspirin increases CBR-HR maximal gain during concurrent muscle mechanoreflex and metaboreflex activation in humans, without affecting CBR-MAP maximal gain (Drew et al., 2012). When viewed together, this may reveal a specific link between TX and metabolite-sensitised muscle mechanoreceptors that influences cardiac vagal activity. Supported by P01 HL096570 (LIS); UL1 RR033184 (LIS).