An impairment of immunity is reported after long-haul flights, and the mild hypobaric hypoxia caused by pressurization in the passenger airline cabin may contribute to it. In this controlled crossover study, the effects of two levels of hypoxia, equivalent to 8000 and 12,000 feet above sea level, on the rhythm of CD3, CD4, and CD8 lymphocytes and plasma concentrations of the immunoglobulins A, G, and M were assessed. Fourteen healthy male volunteers, aged 23 to 39 years, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), simulating an altitude condition at 8,000 feet. This was followed by an additional 8.5 h study four weeks later simulating altitude conditions at 12,000 feet. The variables were assayed every 2 h over two 24 h cycles (control and hypoxic-exposure cycles). No significant effect of hypoxia on the studied circadian immune profiles were found. Therefore, the authors conclude that mild hypobaric hypoxia does not seem to be responsible for any quantitative changes during long-haul flights in the immune assays commonly used in routine clinical medicine practice.