Introduction: The "open window" theory describes the purported short-term suppression of the immune system following an acute bout of endurance exercise, which may lead to an increased susceptibility to upper respiratory illness (URI). Although many studies have found evidence of a decrease in immune function after intense exercise, these studies have not documented the changes in immune function past 2 h after the completion of exercise. It is unclear whether these immune functions return to resting levels before a second bout of exercise on the same day. Methodology: Ten male "A" grade cyclists (age 24.2 ᠵ.3 years; body mass 73.8 ᠶ.5 kg; VO2peak 65.9 ᠷ.1 mL kg-1 min-1) exercised for 2 h at 90% of their second ventilatory threshold. Blood samples were collected before, immediately after, and 2, 4, 6, 8, and 24 h after exercise. Immune variables examined included total leucocyte counts, neutrophil function, lymphocyte subset counts, natural killer (NK) cytotoxic activity, and NK cell phenotypes. Results: Total lymphocyte numbers increased from before to immediately after exercise (p < 0.01), decreased at 2 h after exercise (p < 0.001), and returned to resting level 24 h after exercise. CD4+ T-cell counts increased from before to 4 h (p < 0.05) and 6 h after exercise (p < 0.01), and remained elevated at 24 h after exercise. NK cell numbers decreased significantly from before to 4, 6 and 8 h after exercise (p < 0.05), and returned to resting level by 24 h after exercise. CD56brightCD16- NK cell counts increased from before to immediately after exercise (p < 0.01) and returned to baseline level by 2 h after exercise. NK cytotoxic activity and neutrophil oxidative burst activity did not change significantly after exercise. However, neutrophil cell counts increased from before to immediately after exercise (p < 0.05) and 2 h after exercise (p < 0.01), and returned to resting level by 24 h after exercise. Neutrophil phagocytic function decreased from 2 h to 6 h and 8 h after exercise (p < 0.05). Eosinophil cell counts increased from 2 h to 6 h and 8 h after exercise (p < 0.05). Conclusion: This is the first study to show changes in immune cell counts and function for up to 8 h after exercise. These long-lasting changes in total lymphocyte and NK cell counts and neutrophil phagocytic function following exercise may contribute to the risk of URI associated with intense endurance exercise training in athletes who train more than once a day.