abstract: Biological sex influences exercise performance, largely owing to anatomical and physiological differences in brain areas involved in cognitive motor control and in respiratory and locomotor muscles related to workload. We used near-infrared spectroscopy data to examine sex differences in haemodynamic responses and oxygenation patterns in the prefrontal cortex (PFC), m. intercostales and m. vastus lateralis during incremental exercise in 74 endurance-trained individuals. Changes (Δ) in oxyhaemoglobin (O2-Hb), deoxyhaemoglobin (H-Hb) and tissue saturation index (TSI) were analysed using a two-way ANOVA with the factors ‘sex’ and ‘intensity’. Effect sizes (ES) were also reported by partial eta squared (ηp 2). Interactions were observed for ΔO2-Hb at the PFC [p textless 0.001, ηp 2 = 0.42 (large ES)] and m. intercostales [p textless 0.001, ηp 2 = 0.38 (large ES)], but not at m. vastus lateralis (p = 0.160). For ΔH-Hb, interactions were observed at m. vastus lateralis [p textless 0.001, ηp 2 = 0.35 (large ES)] and the PFC [p = 0.048, ηp 2 = 0.18 (large ES)]. The ΔTSI also showed an interaction at m. vastus lateralis [p textless 0.001, ηp 2 = 0.44 (large ES)] and a trend in the m. intercostales (p = 0.057). Male subjects demonstrated greater oxygen delivery to the brain and increased peripheral deoxygenation, whereas females exhibited greater oxygen extraction in respiratory muscles, despite smaller body surface area. Higher tissue oxygen extraction reflects the capacity to meet local metabolic demands during exercise, enabling the identification of distinct oxygenation patterns between sexes. These findings suggest that sex-specific mechanisms contribute to different patterns of physiological response to exercise. We support the hypothesis that peripheral factors might be more limiting in males, whereas in females central limitations (such as potential reduced oxygen delivery to the PFC owing to possible cerebral vasoconstriction triggered by metabolic reflexes) might play a more prominent role authors: