Several brands of water enriched with O (O-waters) are commercially available and are advertised as wellness and fitness waters with claims of physiological and psychological benefits, including improvement in exercise performance. However, these claims are based, at best, on anecdotal evidence or on a limited number of unreliable studies. The purpose of this double-blind randomized study was to compare the effect of two O-waters (~110 mg O·L) and a placebo (10 mg O·L, i.e., close to the value at sea level, 9-12 mg O·L) on the cardiopulmonary responses and on performance during high-intensity exercise. One of the two O-waters and the placebo were prepared by injection of O. The other O-water was enriched by an electrolytic process. Twenty male subjects were randomly allocated to drink one of the three waters in a crossover study (2 L·day × 2 days and 15 mL·kg 90 min before exercise). During each exercise trial, the subjects exercised at 95.9 ± 4.7% of maximal workload to volitional fatigue. Exercise time to exhaustion and the cardiopulmonary responses, arterial lactate concentration and pH were measured. Oxidative damage to proteins, lipids and DNA in blood was assessed at rest before exercise. Time to exhaustion (one-way ANOVA) and the responses to exercise (two-way ANOVA [Time; Waters] with repeated measurements) were not significantly different among the three waters. There was only a trend ( = 0.060) for a reduction in the time constant of the rapid component of VO kinetics with the water enriched in O by electrolysis. No difference in oxidative damage in blood was observed between the three waters. These results suggest that O-water does not speed up cardiopulmonary response to exercise, does not increase performance and does not trigger oxidative stress measured at rest.