Brief squid Lolliguncula brevis are regularly exposed to fluctuating oxygen levels in their shallow coastal environment. To assess hypoxia resistance, animals were exposed for two hours to ambient oxygen partial pressures (P(o2)) between 19.3 kPa (normoxia) and 6.6 kPa (34.2% air saturation) at 20 ± 1°C. In a second set of experiments, the animals were subjected to a low P(o2) of 2.8 ± 0.3 kPa (14.5 ± 1.6% air saturation) for 15 to 60 min. Subsequently, metabolic, energy and acid-base status were analysed in the mantle tissue. Onset of anaerobic metabolism was observed between 9.4 and 7.9 kPa (48.7 and 40.9% air saturation), reflecting the critical oxygen tension for this species. The formation of octopine and acetate indicates a simultaneous onset of anaerobic metabolism in both the cytosol and the mitochondria during progressive hypoxia. Concomitantly, an intracellular acidosis developed. During exposure to oxygen partial pressures between 19.3 and 6.6 kPa, aerobic and anaerobic processes were sufficient to maintain energy status in the mantle musculature. No significant changes in ATP and phospho-L-arginine (PLA) concentrations were observed. In contrast, both ATP and PLA levels declined significantly after 15 min at an ambient P(o2) of 2.8 ± 0.3 kPa. Concomitantly, the Gibb's free energy change of ATP hydrolysis fell to a minimum value of about -44 kJ · mol-1, a level suggested to reflect limiting energy availability for cellular ATPases. These results indicate, that hypoxia at 2.8 kPa (14.5% air saturation) rapidly takes LolIiguncula brevis to the limits of performance. However, it is probably capable of withstanding longer periods of moderate hypoxia close to 50% air saturation (9.7 kPa), enabling the squids to cope with oxygen fluctuations in their shallow estuarine environment or to dive into hypoxic waters by use of their economic jetting strategy. Nonetheless, the critical P(o2) is considered to be high compared to other hypoxia tolerant animals, an observation likely related to the high metabolic rate of these squids.