Purpose To examine whether the children’s superiority, over adults, to resist fatigue during repeated maximal-efforts depends on their often-cited oxidative advantage, attributed to greater muscle blood flow and O2-delivery. We also investigated the mechanisms underlying child–adult differences in muscle-oxygenation (due to O2-supply or O2-utilization) and examined if there are age-differences in cerebral-oxygenation response (a brain-activation index). Methods Eleven men (23.3 ± 1.8yrs) and eleven boys (11.6 ± 1.1 yrs) performed 15 maximal-effort handgrips (3-s contraction/3-s rest) under two conditions: free-flow circulation (FF) and arterial-occlusion (OCC). Force, muscle-oxygenation (TSImuscle) and cerebral-oxygenation (oxyhemoglobin-O2Hbcerebral; total hemoglobin-tHbcerebral; deoxyhemoglobin-HHbcerebral) were assessed. Results In boys, force declined less (− 26.3 ± 2.6 vs. − 34.4 ± 2.4%) and at slower rate (− 1.56 ± 0.16 vs. − 2.24 ± 0.17%·rep−1) vs. men in FF (p textless 0.01–0.05; d = 0.60–1.24). However, in OCC there were no age-differences in the magnitude (− 38.3 ± 3.0 vs. − 37.8 ± 3.0%) and rate (− 2.44 ± 0.26 vs. − 2.54 ± 0.26%·rep−1) of force decline. Boys compared to men, exhibited less TSImuscle decline in both protocols, and lower muscle VO2 (p textless 0.05). Boys, also, presented a smaller O2Hbcerebral and tHbcerebral rise than men in FF; exercising with OCC increased the O2Hbcerebral and tHbcerebral response in boys. Using MVIC as a covariate in FF condition, abolished boys-men differences in force and TSImuscle decline and O2Hbcerebral rise. Conclusion During repeated maximal-efforts: (i) blood flow is a significant contributor to children’s superiority over adults to resist fatigue; (ii) age-difference in muscle hypoxia/deoxygenation is rather attributed to men’s greater metabolic demand than to lower muscle-perfusion; and (iii) cerebral oxygenation/blood volume increase more in men than boys under free circulation, implying greater brain activation.