Background: Every year, thousands of people travel to high altitude and experience hypoxemia. At high altitude, the partial pressure of oxygen decreases. The aim of this observational study was to determine if there is a relationship between anthropometric features and basic cardiorespiratory variables, including oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP), following acute exposure to high altitude. Materials and Methods: At the 3,466 m top of a cableway station, we installed an automated system for measuring peripheral SpO2, HR, BP, height, weight, and body mass index (BMI). Results: Between January and October 2020, out of 4,874 volunteers (age 39.9 ± 15.4 years, male 54.4%), 3,267 provided complete data (1,808 cases during winter and 1,459 during summer). SpO2 was 86.8% ± 6.8%. At multivariable analysis, SpO2 was significantly associated with age, sex, season, BMI, and HR but not with BP. We identified 391 (12%) subjects with SpO2 ≤80%: they were older, with a higher BMI and HR but without sex or BP differences. Finally, winter season was associated with greater frequency of SpO2 ≤80% (13.3% vs. 10.3%, p = 0.008). Conclusion: Our data show that high BMI, older age, and male sex were associated with greater degrees of hypoxemia following exposure to high altitude, particularly during the winter.