Background: HIV has become a chronic disease. Therefore, the mental health and sleep quality of people living with HIV/AIDS (PLWHA) have become increasingly important issues of concern. Purpose: To explore the sleep quality, depression, anxiety, and self-esteem of PLWHA and the correlation between sleep quality and various related mental-health factors. Methods: A cross-sectional, descriptive, correlational study was conducted at a medical center in southern Taiwan in 2013-2014. Data on the sleep quality, depression, anxiety, and self-esteem of 146 PLWHA cases were collected using a structural questionnaire (the Pittsburgh Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, Zung’s Self-Administered Anxiety Scale, and Rosenberg Self-Esteem Scale). Results: Three-fifths (60.3%) of the cases had poor sleep quality, 50% were inclined toward depression, and 36.3% were inclined toward anxiety, indicating that sleep quality, depression, and anxiety levels in these cases were worse than the general population. Moreover, significant correlations were identified between poor sleep quality and the variables of depression (r = .40, p < .001) and anxiety (r = .53, p < .001). Multiple variate analysis revealed that older age, subjective feelings that HIV significantly influenced personal life, anxiety, and depression were all significant predictors of sleep quality. No significant correlations were found between CD4 (cluster of differentiation 4) lymphocyte count, HIV viral load, or receiving antiretroviral therapy and the variables of sleep quality, depression, anxiety, or self-esteem. Conclusions/Implications for Practice: About half of the PLWHA cases in the present study exhibited poor sleep quality and tendencies toward depression and anxiety. Moreover, sleep quality and mental health factors were found to be not correlated with CD4 lymphocyte count, HIV viral load, or receiving antiretroviral therapy. Therefore, early evaluation of the sleep quality and mental health of people living with HIV/AIDS is recommended in order to provide holistic care.