Analgesics had been suspected of impairing various immune functions either directly or indirectly. Our primary objective was to compare the effects of intravenous (IV) morphine, tramadol, and ketorolac on stress and immune responses in patients who underwent modified radical mastectomy. Patients: Sixty patients randomly assigned to receive IV morphine 5mg (group M, n=20), tramadol 100mg (group T, n=20), or ketorolac 60mg (group K, n=20) at the end of surgery. Methods: Serum cortisol, prolactin were measured immediately, 40 minutes, and 24 hours postoperatively. Expressions of peripheral T lymphocytes (CD3+, CD3+CD4+, CD3+CD8+) and natural killer cells (CD3+, CD56+) were measured as percentages of total lymphocytes by flow cytometry immediately, 90 minutes, and 24 hours postoperatively. Results: After 40 minutes, cortisol level increased but prolactin decreased significantly (P=0.001), then both decreased after 24 hours (P=0.001) compared with baseline within the 3 groups. CD3, CD4, CD8, and CD56 significantly decreased at 90 minutes and 24 hours (Pr0.033) compared with baseline in the 3 groups. CD4, CD8, and CD56 significantly decreased in group M, compared with group T and K (Pr0.016) and CD3, CD8, and CD56 in group T compared with group K at 90 minutes (Pr0.024) postoperatively. After 24 hours, CD4, and CD8 decreased in group M compared with group T (Pr0.048) and CD4 and CD56 in groups M and T compared with group K (Pr0.049). Conclusions: IV morphine, tramadol, and ketorolac suppressed stress and immune responses. Ketorolac was the least immunosuppressive among the 3 drugs.