Objective: The effects of knee-high socks that applied different levels of compression (0, 10, 20, 30 and 40 mmHg) on various cardio-respiratory and metabolic parameters during submaximal running were analysed. Methods: Fifteen well-trained, male endurance athletes (age: 22.2 +/- 1.3 years; peak oxygen uptake: 57.2 +/- 4.0 mL/minute/kg) performed a ramp test to determine peak oxygen uptake. Thereafter, all athletes carried out five periods of submaximal running (at approximately 70% of peak oxygen uptake) with and without compression socks that applied the different levels of pressure. Cardiac output and index, stroke volume, arteriovenous difference in oxygen saturation, oxygen uptake, arterial oxygen saturation, heart rate and blood lactate were monitored before and during all of these tests. Results: Cardiac output (P = 0.29) and index (P = 0.27), stroke volume (P = 0.50), arteriovenous difference in oxygen saturation (P = 0.11), oxygen uptake (P = 1.00), arterial oxygen saturation (P = 1.00), heart rate (P = 1.00) and arterial lactate concentration (P = 1.00) were unaffected by compression (effect sizes = 0.00-0.65). Conclusion: This first evaluation of the potential effects of increasing levels of compression on cardio-respiratory and metabolic parameters during submaximal exercise revealed no effects whatsoever.