A triathlon is an endurance event in which athletes need an efficient hydration strategy since hydration is restricted at different stages. However, it seems that seawater intake can be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to evaluate the efficacy of seawater hydration during a triathlon on cytokine production. Fifteen trained male triathletes (age = 38.8 ± 5.62 years old; BMI = 22.58 ± 2.51 kg/m2) randomly performed three triathlons, one of them consuming seawater (Totum SPORT, Laboratories Quinton International, S.L., Valencia, Spain), the other one consuming tap water ad libitum, and the last a physiologic saline solution as placebo. The triathlon consisted of an 800 m swim, a 90 km bike ride, and a 10 km run. Blood samples were taken at rest and after training, where markers of inflammation, hemoglobin, and hematocrit concentration were assessed. While the seawater was not ergogenic, it significantly increased the release of IL-6 and apelin post-exercise. However, no differences were found between the fractalkine, IL-15, EPO, osteonectin, myostatin, oncostatin, irisin, FSTL1, osteocrin, BDNF, and FGF-21 values over those of the placebo group. The present study demonstrates that hydration with seawater stimulates myokine production, which could lead to improved performance recovery after exercise.