Supplementary oxygen is commonly administered in current medical practice. However, attention has recently been drawn to the potentially disadvantageous hemodynamic consequences in certain patients. Possible mechanisms underlying the cardiovascular responses to acute hyperoxia are unclear. The effects of acute oxygen administration on heart rate, blood pressure, cardiac output, systemic vascular resistance, and baroreflex sensitivity were studied in a series of randomised, placebo-controlled studies in healthy individuals, using validated, non-invasive techniques. The effects of oxygen administration on forearm blood flow responses to locally administered acetylcholine, an endothelium-dependent vasodilator, sodium nitroprusside, an endothelium-independent vasodilator, and l-NG-monomethylarginine, a nitric oxide synthase inhibitor, were studied using venous occlusion plethysmography. Oxygen administration for 1 hour caused a reduction in heart rate (P < 0.01) and cardiac index (P < 0.05), and an increase in mean arterial pressure (P < 0.01), systemic vascular resistance (P < 0.05), large artery stiffness (P < 0.05), and baroreflex sensitivity (P < 0.05). There were no effects on vascular responses in the isolated forearm bed. These findings indicate that oxygen administration causes acute effects on cardiovascular function, which might be important in the context of acute illness.