Objective: Open water swimming (OWS) is an endurance sport. Nitric oxide (NO) is a vasodilator gas, therefore it is related to endurance. Physiological stress levels of OWS on children are unknown. The purposes of this study were to investigate the physiological responses to 5000 m OWS and its relation with serum NOx (nitrite plus nitrate) levels in children. Material and Methods: Trained OWS athletes (9 males and 5 females; age=13.8±1.12 years) participated in the study. Serum NOx, oxidative stress index (OSI): total antioxidant status (TAS)/total oxidant stress status (TOS) ratio, muscle damage markers (MDM): serum creatine kinase (CK), aspartate aminotransferase (AST) activity, leucocyte counts and serum glucose (GLU) levels were determined before and after the OWS. Lactate (La), whole blood glucose (WGLU) analyses were done from the fingertip blood samples and heart rate (HR) was measured after every 1000 m. Results: After 5000 m OWS, HR and La levels were recorded as 166 beat/min and 2.95 mM. The results indicated that MDM significantly increased (p<0.01), and OSI significantly decreased however there were no significantly changes in TAS, NOx and serum glucose (GLU) values. Basal NOx levels was only related to CK (r=-0.529, p=0.052), but not other parameters. Conclusion: 5000 m OWS exercise induced a moderate physiological stress without any oxidative stress, hypoglycemia and health risk for the investigated parameters risk. Although this exercise did not increase blood NOx levels, the negative relationship between basal NOx and CK parameters may show the anti-inflammatory role of NO during OWS exercises in the children.