Background/Aims: Water diuresis usually increases medullary oxygenation as a result of increased medullary synthesis of prostaglandins, but it is not clear whether this involves activation of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2). Methods: The effects of celecoxib, a selective inhibitor of COX-2, and of ibuprofen, a non-specific inhibitor of COX-1 and COX-2, upon renal oxygenation during water diuresis were studied in a double-blind, prospective manner in 13 young women (age 24–34 years) using blood-oxygen level dependent magnetic resonance imaging. Celecoxib 200 mg b.i.d. for 4 days was compared with ibuprofen 80 mg b.i.d. for 4 days and with a placebo. Results: There was no effect of either drug on urinary volume, urinary osmolal concentration, or creatinine clearance. Water diuresis alone elicited a significant increase in oxygenation in borderline areas between cortex and medulla, which was eliminated by celecoxib or ibuprofen. Conclusion: Renal medullary oxygenation is improved by water diuresis in normal young women in a way that is blocked by a selective inhibitor of COX-2 as well as non-selective cyclooxygenase inhibitors. Selective COX-2 may be expected to have significant effects on renal functions.