Because conjunctival vessels are affected by sickle cell disease, we wanted to see if conjunctival PO2 (partial oxygen tension) and temperature were also affected and if these measurements could aid in managing these patients. Conjunctival PO2 and temperature in 23 asymptomatic homozygous patients with sickle cell anemia did not differ significantly from those in age-matched controls. However, 12 subjects in painful sickle cell crisis had a significantly lower conjunctival PO2 than before crisis despite no significant change in hematocrit and conjunctival temperature. Supplemental oxygen therapy significantly increased conjunctival PO2. When supplemental oxygen was removed, conjunctival PO2 decreased to the admission level despite clinical improvement. This finding supports the use of supplemental oxygen in treating crisis. Measuring conjunctival PO2 can give clinicians an assessment of the effect of sickle cell disease on a peripheral capillary bed and may provide the first objective method to reliably diagnose acute painful sickle cell crisis.