During the last decades, the number of lowland children exposed to high altitude (HA) has increased drastically. Several factors may influence the development of illness after acute HA exposure on children and adolescent populations, such as altitude reached, ascent velocity, time spent at altitude and, especially, their age. The main goal of this study was to evaluate the resting cardiorespiratory physiological and submaximal exercise responses under natural HA conditions by means of the six-minute walking test (six MWT). Secondly, we aimed to identify the signs and symptoms associated with acute mountain sickness (AMS) onset after acute HA exposure in children and adolescents. Forty-two children and adolescents, 18 boys and 24 girls aged from 11 to 15 years old, participated in this study, which was performed at sea level (SL) and during the first 42 hours at HA (3330 m). The Lake Louise score (LLS) was recorded in order to evaluate the evolution of AMS symptoms. Submaximal exercise tests (six MWT) were performed at SL and HA. Physiological parameters such as heart rate, systolic and diastolic blood pressure, respiratory rate and arterialized oxygen saturation were measured at rest and after ending exercise testing at the two altitudes. After acute HA exposure, the participants showed lower arterial oxygen saturation levels at rest and after the submaximal test compared to SL (p < 0.001). Resting heart rate, respiratory rate and diastolic blood pressure presented higher values at HA (p < 0.01). Moreover, heart rate, diastolic blood pressure and dyspnea values increased before, during and after exercise at HA (p < 0.01). Moreover, submaximal exercise performance decreased at HA (p < 0.001). The AMS incidence at HA ranged from 9.5% to 19%, with mild to moderate symptoms. In conclusion, acute HA exposure in children and adolescent individuals produces an increase in basal cardiorespiratory parameters and a decrement in arterial oxygen saturation. Moreover, cardiorespiratory parameters increase during submaximal exercise at HA. Mild to moderate symptoms of AMS at 3330 m and adequate cardiovascular responses to submaximal exercise do not contraindicate the ascension of children and adolescents to that altitude, at least for a limited period of time.