The aim of this study was to investigate the impact of exercise-induced hypoxaemia (EIH) developed at sea-level on exercise responses at moderate acute altitude. Methods Twenty three subjects divided in three groups of individuals: highly trained with EIH (n = 7); highly trained without EIH (n = 8) and untrained participants (n = 8) performed two maximal incremental tests at sea-level and at 2,150 m. Haemoglobin O2 saturation (SpO2), heart rate, oxygen uptake (VO2) and several ventilatory parameters were measured continuously during the tests. Results EIH athletes had a drop in SpO2 from 99 ± 0.8% to 91 ± 1.2% from rest to maximal exercise at sea-level, while the other groups did not exhibit a similar decrease. EIH athletes had a greater decrease in VO2max at altitude compared to non-EIH and untrained groups (-22 ± 7.9%, -16 ± 5.3% and -13 ± 9.4%, respectively). At altitude, non-EIH athletes had a similar drop in SpO2 as EIH athletes (13 ± 0.8%) but greater than untrained participants (6 ± 1.0%). EIH athletes showed greater decrease in maximal heart rate than non-EIH athletes at altitude (8 ± 3.3 bpm and 5 ± 2.9 bpm, respectively). Conclusion EIH athletes demonstrated specific cardiorespiratory response to exercise at moderate altitude compared to non-EIH athletes with a higher decrease in VO2max certainly due to the lower ventilator and HRmax responses. Thus EIH phenomenon developed at sea-level negatively impact performance and cardiorespiratory responses at acute moderate altitude despite no potentiated O2 desaturation