In Y men, breathing 40%O2, and inhibition of COX with aspirin, alone or together caused similar attenuation of post-contraction hyperaemia evoked by static contraction, indicating that the dilator action of prostaglandins (PGs) is O2-dependent1. Further, breathing 40%O2 during a 7min recovery period from static contraction at 100% maximum voluntary contraction to exhaustion (MVE), reduced fatigue in a 2nd 100%MVE2. Recently, in both Y and O men, 40%O2 or COX inhibition attenuated post-contraction hyperaemia by ~60 and 30% respectively and venous efflux of PGI2 and PGE23. Skeletal muscle fibres have COX activity and generate PGE2 which increases relaxation speed of oxidative muscle fibres in vitro4. We hypothesised that 40%O2 or COX inhibition alone or together would differentially affect muscle force generation and/or recovery from fatigue in Y and O men. Experiments were performed on recreationally active 10 Y and 11 O men (20-25; 66-78 yr) who performed 2 static handgrip contractions at 100%MVE separated by 7 min recovery in a single blind cross over study after placebo with air breathing throughout (P), or with 40%O2 during recovery (O2), after aspirin (600mg p.o) with air (A), or after A with 40%O2 in recovery (A/O2). In Y, tension time integral (TTI) was 46.4±4.4 in Contraction 1 and fell to 30.2±2.9* in Contraction 2 in P, but was maintained at 42.2±4.4 and 40.0±4.9 kN.s respectively in O2 (*P<0.05, RM-ANOVA; Contraction 2 vs 1). Further, TTI fell from 44.4±3.5 to 29.9±2.4* in A, but was maintained at 42.5±3.2 and 39.5±2.9 kN.s in A/O2. Peak force (PF) in Y was 504.2±38.5 vs 434.58±43.2, 510.1±36.3 vs 476.8±39.2, 467.9±45.1 vs 406.1±48.1 and 486.6±34.3 vs 443.4±26.5N in P, O2, A and A/O2 respectively. As expected, “work done” in Contraction 1 in O males was less than Y in all conditions: TTI was 35.8±3.8, 33.1±4.7, 35.7±3.4 and 35.5±6.4 kN.s for P, O2, A and A/O2 respectively (P<0.05). As in Y, TTI in Contraction 2 fell to 24.5±2.8* in P, but was maintained at 29.7±2.7 in O2. However, TTI fell to 29.4±3.2* and 28.6±4.0 (P=0.07) kN.s in A and A/O2 respectively. PF in O was 210.1±19.6 vs 207.8±19.3, 207.5±20.3 vs 206.3±20.4, 206.6±19.1 vs 197.5±16.3 and 203.1±18.8 vs 202.6±19.2N (P<0.05 vs Y). These results indicate that in Y men, breathing 40%O2 in recovery from MVE provides sufficient additional O2 to muscle fibres to reduce fatigue in a second contraction, even during COX inhibition, which reduces muscle blood flow. By contrast, in healthy O men, breathing 40%O2 in recovery is similarly beneficial, but uptake of sufficient O2 to improve recovery from fatigue is more easily compromised when O2 delivery is attenuated by COX inhibition. PGs generated during contraction do not seem to affect muscle contraction or recovery from fatigue in Y or O men.