We investigated the cortisol and cytokine responses to surgical stress in the different age groups of pediatric patients. This study included 19 neonates (0-6 days old, group I), 19 infants (1-11 months old, group II), and 20 pre-school children (1-5 years old, group III), undergoing major thoracic and abdominal surgery. We obtained blood samples preoperatively and 0, 3, 6, 12, and 24 h postoperatively to measure the plasma levels of C-reactive protein (CRP), cortisol, interleukin (IL)-6, and IL-10. The plasma CRP level in each group reached a peak value on postoperative day 2; however, the peak value was significantly lower in group I than in groups II or III (I vs II, III; p=0.0134, p=0.0017, respectively). The plasma cortisol level in each group reached a peak value just after surgery; however, the peak value was also significantly lower in group I than in groups II or III (I vs II, III; p<0.001, p=0.0104, respectively). The plasma IL-6 level in each group reached a peak level hours postoperatively; however, the peak values in groups I and II were higher than in group III (I, II vs III; p=0.003, p=0.0458, respectively). The plasma IL-10 level in each group reached a peak value just after surgery and did not differ among the three groups. The endocrine and cytokine responses to the surgical stress vary among the different age groups of pediatric patients.