Whether mental performance is affected by slowly progressive moderate dehydration induced by water deprivation has not been examined previously. Therefore, objective and subjective cognitive-motor function was examined in 16 volunteers (8 females, 8 males, mean age: 26 yr) twice, once after 24 h of water deprivation and once during normal water intake (randomized cross-over design; 7-day interval). Water deprivation resulted in a 2.6% decrease in body weight. Neither cognitive-motor function estimated by a paced auditory serial addition task, an adaptive 5-choice reaction time test, a manual tracking test, and a Stroop word-color conflict test nor neurophysiological function assessed by auditory event-related potentials P300 (oddball paradigm) differed (P > 0.1) between the water deprivation and the control study. However, subjective ratings of mental performance changed significantly toward increased tiredness (+1.0 points) and reduced alertness (-0.9 points on a 5-point scale; both: P < 0.05), and higher levels of perceived effort (+27 mm) and concentration (+28 mm on a 100-mm scale; both: P < 0.05) necessary for test accomplishment during dehydration. Several reaction time-based responses revealed significant interactions between gender and dehydration, with prolonged reaction time in women but shortened in men after water deprivation (Stroop word-color conflict test, reaction time in women: +26 ms, in men: -36 ms, P < 0.01; paced auditory serial addition task, reaction time in women +58 ms, in men -31 ms, P = 0.05). In conclusion, cognitive-motor function is preserved during water deprivation in young humans up to a moderate dehydration level of 2.6% of body weight. Sexual dimorphism for reaction time-based performance is present. Increased subjective task-related effort suggests that healthy volunteers exhibit cognitive compensating mechanisms for increased tiredness and reduced alertness during slowly progressive moderate dehydration.