Cancer treatment is known to have significant immuno-suppressive/dysregulatory effects. Psychological distress and depression, which often accompany cancer diagnosis and treatment, can also suppress or dysregulate endocrine and immune function. Cell-mediated immunity (CMI) is critical for protection against a host of pathogens to which cancer patients may be particularly susceptible. CMI is also important for defense against some tumors. This study explored relationships among depressive symptoms, cortisol secretion, and CMI responses in 72 women with metastatic breast cancer. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). Saliva was sampled throughout the day over a 3-day period to obtain a physiologic index of diurnal cortisol concentrations and rhythmicity, which is associated with breast cancer survival time. CMI for specific antigens was measured following intradermal administration of seven commonly encountered antigens (tuberculin, tetanus, diphtheria, Streptococcus, Candida, Trichophyton, and Proteus). Analyses adjusting for relevant medical and treatment variables indicated that women reporting more depressive symptoms showed suppressed immunity as measured by lower average induration size. Women with higher mean diurnal cortisol concentrations also showed suppressed immunity as indicated by a decreased number of antigens to which positive reactions were measured. This study highlights the relationships among depression, stress, and immune function in the context of advanced breast cancer.