Our aim was to evaluate the chronic effects of training and competition during a 4-month season on immune response in professional volleyball players. Players took part in an incremental maximal cycling test at the beginning and at the end of the season. As control group, subjects with regular recreational activity were selected. Blood samples were obtained at rest, immediately after the exercise test, and after 30 min recovery. Volleyball players have similar basal levels of erythrocytes, hematocrit, hemoglobin, and total protein and urate than controls and higher levels of creatinine and activities of AST, ALT, and GGT. Maximal incremental exercise test significantly increased erythrocyte counts, hematocrit, and blood hemoglobin levels in volleyball players. T- and B-lymphocytes significantly increased after exercise test and were maintained high during recovery. Cortisol levels were significantly increased immediately after exercise and during recovery with respect to basal values. Basal and post-exercise cortisol levels were significantly higher at the final of season than at the beginning. Serum levels of immunoglobulins (IgG, IgA, and IgM) and complement fractions (C3, C4) were unaffected by the volleyball season. The IgG and IgM levels were significantly higher after exercise and recovery than basal levels. Maximal exercise test induced an acute phase/inflammatory response characterized by increased circulating lymphocytes, antibody response, and cortisol levels. Competition season increases cortisol concentration indicative of accumulated stress intensity.