Background: The pathophysiology underlying acute mountain sickness (AMS) and excessive hypoxemia at high altitudes is not fully understood. Previous work by our group has demonstrated a significant association between urinary measures of dehydration and bicarbonate retention in subjects developing excessive hypoxemia and AMS at high altitudes. To further characterize these findings, we returned to our original testing site to examine the hypothesis that subjects with lower levels of oxygen saturation and/or AMS would possess higher levels of venous bicarbonate. Methods: Medical history inquiry, clinical examination, Lake Louise scoring, and the collection of venous levels of bicarbonate concentration and base excess were performed on 52 lowland-dwelling persons after they completed a religious pilgrimage in the Nepal Himalayas to approximately 4,250 m. Results: Oxygen saturation levels were strongly and inversely correlated with serum levels of venous bicarbonate and base excess, whereas AMS and Lake Louise scores were not associated with these measures of alkalosis. Conclusions: Our data suggest an association between measures of serum bicarbonate anion retention and decreasing oxygen saturation. Our data do not demonstrate an association between AMS or Lake Louise scores and measures of serum bicarbonate level. We propose that excessive hypoxemia at high altitudes may be associated with a compromised ability of the kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.