Decrease in peripheral oxygen delivery may impact exercise performance in athletes with exercise-related arterial oxygen desaturation (ERD). We evaluated whether sodium bicarbonate ingestion would be effective to reduce ERD and what is the consequences upon exercise performance. Seventy highly trained athletes performed an incremental treadmill cardiopulmonary exercise test (incCPX) and a high intensity constant speed test (ctCPX) on separate days. Subjects who developed ERD by pulse oximetry were randomly allocated to oral sodium bicarbonate or placebo during 5 days. At the end of treatment subjects repeated both tests. ERD prevalence was 33% during the incCPX (17 % severe, 48% moderate and 35% mild) and 34% (5 % severe, 37% moderate and 58% mild) in the ctCPX. Athletes who developed ERD have greater aerobic capacity (incCPX) and endurance time (ctCPX). Active treatment, but not placebo, reduced ERD during ctCPX (P<0.05). However, there were no significant positive effects on main parameters of aerobic function and endurance exercise capacity (P>0.05). Sodium bicarbonate was effective in lessening ERD during ctCPX in athletes. However, this intervention failed to improve maximal and submaximal exercise capacity in these subjects.