Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep. Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1–2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep. Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ± 10.9 to 130.6 ± 12.3, p = 0.0032 and from 78.8 ± 6.7 to 81.8 ± 7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ± 12.4 to 107.4 ± 12.7, p = 0.0028, and from 62.0 ± 8.2 to 65.8 ± 8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40–2.90) to 5.4 (2.90–10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI. Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patterns during sleep with gender and age-related differences. Further studies are needed to explore the clinical relevance of these findings. •Acute exposure to moderate altitude leads to an increase in systolic and diastolic blood pressure.•Sleep breathing disturbances, mostly central hypopneas, appear in this condition.•No association was found between size of blood pressure changes and hypopnea entity.•These changes are evident mainly in people aged over 40 years.