In the course of their missions or training, alpinists, but also mountain combat forces and mountain security services, professional miners, aircrew, aircraft and glider pilots and helicopter crews are regularly exposed to altitude without oxygen supplementation. At altitude, humans are exposed to systemic environmental hypoxia induced by the decrease in barometric pressure (<1,013 hPa) which decreases the inspired partial pressure of oxygen (PIO2), while the oxygen fraction is constant (equal to approximately 20.9%). Effects of altitude on humans occur gradually and depend on the duration of exposure and the altitude level. From 1,500 m altitude (response threshold), several adaptive responses offset the effects of hypoxia, involving the respiratory and the cardiovascular systems, and the oxygen transport capacity of the blood. Fatigue and cognitive and sensory disorders are usually observed from 2,500 m (threshold of prolonged hypoxia). Above 3,500 m (the threshold for disorders), the effects are not completely compensated and maladaptive responses occur and individuals develop altitude headache or acute altitude illness [Acute Mountain Sickness (AMS)]. The magnitude of effects varies considerably between different physiological systems and exhibits significant inter-individual variability. In addition to comorbidities, the factors of vulnerability are still little known. They can be constitutive (genetic) or circumstantial (sleep deprivation, fatigue, speed of ascent.). In particular, sleep loss, a condition that is often encountered in real-life settings, could have an impact on the physiological and cognitive responses to hypoxia. In this review, we report the current state of knowledge on the impact of sleep loss on responses to environmental hypoxia in humans, with the aim of identifying possible consequences for AMS risk and cognition, as well as the value of behavioral and non-pharmacological countermeasures.