Objective: To assess the effect of lifeguard fatigue on the quality of cardiopulmonary resuscitation (CPR) after water rescue. Methods: Sixty professional lifeguards (30 men, 30 women) trained at the University of A Coruna and the University of Vigo in Spain participated in 2 tests. In the first test, the participants were rested when they performed 4 minutes of CPR. In the second, they undertook 4 minutes of CPR immediately after rescuing a mannequin from the water. The Resusci Anne Skill Reporter mannequin (Laerdal) was used to produce a computerized record of the total number of compressions and ventilations as well as the percentages of each type of maneuver the lifeguards performed correctly and incorrectly. Results: In both rested and fatigued conditions, the participants performed fewer correct compressions (absolute numbers and percentages) as CPR continued over the assigned minutes. After a water rescue, the total number of compressions increased (when rested, 75.4; when fatigued, 84.2) (P<.001), while the percentage of correct ventilations decreased (rested, 55.1%; fatigued, 34.7%; (P<.001) and correct compressions (rested, 77.5%; fatigued, 63.6%) (P<.001). Conclusions: Lifeguard fatigue after a water rescue negatively affects CPR quality. We recommend that a rested lifeguard should perform CPR whenever possible.