Precooling, or a reduction in core temperature (Tc) has been demonstrated to be a potent enhancer of endurance running performance, however there is no known mechanism for this improvement. By holding the exercise workload constant, changes in variables such as running economy (RE), heart rate, and ventilation (VE) can be determined as a result of precooling. Improved running economy, or a reduced oxygen cost of a specific workload, is linked to improved exercise performance. Purpose: To determine the changes in flexibility, RE, heart rate, VE, and Tc during running at a constant workload following cool water immersion and to determine any sex-specific responses. Methods: Fourteen well-trained runners (8 males and 6 females) completed four treadmill runs at a sex-specific velocity (8.0 mph for females and 8.6 mph for males). The first two runs served as accommodation trials. The third and fourth runs were preceded by either cool water immersion (24.8oC) for 40 minutes or quiet sitting. Oxygen consumption, heart rate, Tc, VE, and flexibility were measured during both experimental trials. Results: Running economy did not change as a result of the precooling treatment, whereas Tc and heart rate were reduced by 0.4oC and 5 beats per minute, respectively. Minute ventilation was reduced in the female subjects only (1.4 liters/min). Sex differences were apparent in Tc, heart rate, VE, and flexibility response. Conclusion: While the precooling procedure was effective in reducing Tc and heart rate, RE did not change. Thus, improvements in RE cannot explain the dramatic enhancements of endurance running performance that often occur post-cooling. Differences between male and female subjects in response to precooling were identified, most notably in VE.