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To determine the effects of different oxygen tensions (Po2) on glucose measurements with glucose dehydrogenase (GD)-based and glucose oxidase (GO)-based test strips, to quantitate changes in glucose measurements observed with different Po2 levels, and to discuss the potential risks of oxygen-derived glucose errors in critical care.Venous blood from healthy volunteers was tonometered to create different oxygen tensions simulating patient arterial Po2 levels. Venous blood from diabetic patients was exposed to air to alter oxygen tensions simulating changes in Po2 during sample handling. Whole-blood glucose measurements obtained from these samples with six glucose meters were compared with reference analyzer plasma glucose measurements. Glucose differences were plotted vs. different Po2 levels to identify error trends. Error tolerances were as follows: a) within ±15 mg/dL of the reference measurement for glucose levels ≤100 mg/dL; and b) within ±15% of the reference measurement for glucose levels >100 mg/dL.Five healthy volunteers in the bench study and 11 diabetic patients in the clinical study.In the bench study, increases in Po2 levels decreased glucose measured with GO-based amperometric test strips, mainly at Po2 levels >100 torr. At nearly constant glucose concentrations, glucose meter systems showed large variations at low (39 torr) vs. high (396 torr) Po2 levels. Glucose measured with GD-based amperometric and GO-based photometric test strips generally were within error tolerances. In the clinical study, 31.6% (Precision PCx), 20.2% (Precision QID), and 23.0% (Glucometer Elite) of glucose measurements with GO-based amperometric test strips, 14.3% (SureStep) of glucose measurements with GO-based photometric test strips, and 4.6% (Accu-Chek Advantage H) and 5.9% (Accu-Chek Comfort Curve) of glucose measurements with GD-based amperometric test strips were out of the error tolerances.Different oxygen tensions do not significantly affect glucose measured with the GD-based amperometric test strips, and have minimal effect on GO-based photometric test strips. Increases in oxygen tension lowered glucose measured with GO-based amperometric test strips. We recommend that the effects of different oxygen tensions in blood samples on glucose measurements be minimized by using oxygen-independent test strips for point-of-care glucose testing in critically ill and other patients with high or unpredictable blood Po2 levels.