Two cross-sectional studies in a high altitude region of Perú evaluated the role of pulse oximetry for detection of silicosis in high-altitude miners. In study one, exercise pulse oximetry and chest radiographs were used to evaluate 343 silica-exposed miners and 141 unexposed subjects for evidence of silicosis. Study 2 investigated the association between exercise oxygen saturation and silicosis in 32 non-silicotic and 65 silicotic miners. In study one, age (Odds Ratio [OR] 1.10, 95% Cofidence Interval (CI) 1.07-1.12) and resting oxygen saturation (OR 0.95, 95%CI 0.90-0.99) were associated with silicosis. In study two, years of mining employment (OR 1.14, 95%CI 1.05-1.23) and exercise oxygen saturation at 30% maximum heart rate (OR 0.86, 95%CI 0.75-0.99) were associated with silicosis. Hypoxemia at rest and with exercise is associated with silicosis in high altitude miners. Pulse oximetry should be further investigated as a screening tool for silicosis at high altitudes.