Swimming is a popular youth sport that is considered beneficial for cardiovascular fitness. However, the potential inflammatory outcomes of high intensity swimming in younger swimmers are unclear, as is the response of irisin, a myokine released during exercise with anti-inflammatory properties. This study compared the plasma concentrations of interleukins 1-beta (IL-1β), 6 (IL-6), 10 (IL-10), tumor necrosis factor alpha (TNF-α) and irisin in response to intense swimming between adolescent and adult male swimmers. Thirty-two swimmers (16 adolescents, 14 ± 1 years; 16 adults, 21.5 ± 3.1 years) completed a high intensity interval swimming trial. At rest, only TNF-α was higher (33%, p < 0.05) in adolescents compared with adults. There was an overall significant increase in IL-1β from pre- to post-swimming (3% in adolescents, 24% in adults), but no significant interaction. IL-10 significantly increased in both groups (+34% in adolescents, +56% in adults). IL-6 and TNF-α increased significantly (+32% and +26%, respectively) in adults, but not in adolescents (+2% and −9%, respectively). Adults showed a small, but significant decrease in irisin (−5%), with no change in adolescents. The lack of an IL-6, TNF-α and irisin response to intense swimming in adolescent swimmers may suggest a blunted inflammatory and myokine response following high intensity exercise in trained youth.