Background: In 1999, Basnyat et al. published preliminary data demonstrating an inverse correlation between hydration status and acute mountain sickness during an epidemiological study performed in the vicinity of Mount Everest. To expand on these findings, we have returned to the Langtang area of the Nepal Himalaya to perform more specific studies of altitude illness related to dehydration and hypoxemia using urine studies, pulse oximetry, and physical examination. Hypothesis: Dehydration will incite physiological changes aimed at the preservation of vascular volume homeostasis characterized by the production of sodium and water sparing hormones. As sodium is reabsorbed in the kidney, bicarbonate anion is also reabsorbed resulting in insufficient bicarbonate anion excretion by the kidney leading to an incomplete compensation for altitude induced hypocapnic alkalosis and the development of clinical disease. Methods: Estimates of intravascular volume (urine specific gravity), oxygen saturation (pulse oximetry), urinary bicarbonate excretion (urine pH), and AMS (Lake Louise Score) were collected from Hindu pilgrims at 4243 m during an annual sacred festival at Lake Gosinkunda. Results: Worsening altitude illness approximated by increasing Lake Louise Score was associated with increasing urine specific gravity (p = 0.043), decreasing oxygen saturation (p = 0.020), and decreasing urine pH (p = 0.040) after rapid ascent to 4243 m. Conclusions: Worsening altitude illness, indicated by increasing Lake Louise score, was associated with increasing measures of dehydration, hypoxemia, and urine acidity.