With decreasing mortality, the quality of life, spiritual needs, and mental health of breast cancer patients have become increasingly important. Demoralization is a poor prognostic factor for cancer patients. The extent of demoralization in breast cancer patients and its association with these factors remains unclear. This cross-sectional study was conducted at a Taiwanese medical center. We enrolled 121 participants (34 with high demoralization and 87 with low demoralization, as per the Mandarin Version of Demoralization Scale). High demoralization was associated with reduced quality of life, sleep quality, and spiritual interests. Multivariate analyses revealed that the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ≥ 62.5 (OR = 0.21, p = 0.002) and Spiritual Interests Related to Illness Tool Chinese Version ≥ 3.66 (OR = 0.11, p < 0.001) were associated with low demoralization. Demoralized patients with depression had a poorer quality of life and sleep quality. Although not statistically significant, depressed and demoralized participants were at a higher risk of suicide. Cancer patients with both depression and demoralization had the worst prognosis. Breast cancer patients exhibited demoralization when they had unmet bio-psycho-social-spiritual needs. An early assessment of demoralization may improve holistic healthcare for breast cancer patients.