Introduction: Chronic intermittent hypoxia (CIH) is a feature of respiratory diseases such as obstructive sleep apnoea and apnoea of prematurity. There is a relative paucity of information on the effects of CIH on respiratory muscle physiology despite the clinical relevance. We have shown that CIH causes an age- and sex-dependent impairment of upper airway dilator muscle. The intensity, duration and pattern of CIH exposure are all key determinants of the respiratory muscle phenotype. Recently we reported that CIH exposure during early life causes upper airway dilator muscle weakness, an effect that persists for several weeks upon return to normoxia. Aim: We wished to determine 1) if neonatal exposure to CIH (nCIH) persists into adulthood and 2) if nCIH increases sensitivity to CIH exposure during adulthood. Methods: Six Wistar litters (with respective dams) were exposed to alternating bouts of hypoxia (5% O2 at the nadir) and normoxia (21% O2) for 12 cycles per hour, 8h/day for 3 weeks from the first day of life (a paradigm that causes sternohyoid dysfunction in neonatal but not adult animals). Sham experiments (continuous normoxia) were run in parallel. The litters were then returned to normoxia for 10 weeks. At this point, rats were treated with CIH for 3 weeks or normoxia. All groups were studied at 16 weeks. Sternohyoid tissue was harvested for functional assessment. Contractile and endurance properties of the muscle were determined in an in vitro isometric bath preparation in Krebs solution gassed with 95%O2/5%CO2 at 35°C. Results: At 16 weeks, sternohyoid force-frequency relationship in nCIH rats was not significantly different from the sham group (P>0.05; 2-way ANOVA) i.e. muscle weakness had fully recovered. Adult exposure to CIH had no effect on sternohyoid function. However, in nCIH rats re-treated with CIH the sternohyoid muscle was weaker (P=0.016). CIH had no effect on sternohyoid muscle endurance. Conclusion: CIH exposure in early life causes airway dilator muscle weakness that persists for several weeks in normoxia but recovers in adulthood. However, repeat exposure to the same CIH paradigm – that in-of-itself has no effect on adult muscle – is sufficient to cause muscle weakness in nCIH rats highlighting a persistent susceptibility (‘deficit memory’) to CIH in nCIH muscle. The upper airway dilator muscles play a crucial role in the breath-by-breath control of airway patency. A similar phenotype in human infants exposed to CIH, such as that occurring in apnoea of prematurity, could lead to long-term susceptibility of the upper airway muscles to hypoxia in later life. We speculate that nCIH could increase the propensity for airway collapse in mature adults. Our data may have relevance to the association of apnoea of prematurity in infants with obstructive apnoea in later life.