Background: HIV/AIDS pandemic has brought huge demands on the healthcare workforce worldwide. Nurses play a critical role in caring for persons living with HIV/AIDS (PLWHA). Inadequate care and discrimination due to negative attitudes of nurses caring for persons living with HIV/AIDS will not only affect the patients, but will adversely affect the fight to halt the pandemic. The objective of this study was to determine nurses’ knowledge and attitude to the care of HIV/AIDS patients in South East, Nigeria.Methods:Descriptive survey design, with the aid of five-point Likert questionnaire administered on 240 nurses caring for PLWHA in University of Nigeria Teaching Hospital Enugu, Nigeria was used.Results: Majority of the respondents had good knowledge of HIV/AIDS. There were significant relationships between the age (P<0.05), marital status (P<0.05), professional cadre of the respondents (P<0.05) and their level of knowledge. 227 (94.6%) of the respondents had positive attitude towards the care of PLWHA. Factors that negatively influenced nurses’ attitude in caring for PLWHA include fear of contagion 56 (82.4%), social stigma 10 (14.7%), culture/religion 6 (8.8%). There were significant relationships between the professional cadre of nurses (P<0.05), knowledge about HIV/AIDS (P<0.05) and their attitude towards the care of HIV/AIDS patients.However, there were no significant relationships between the nurses' marital status (P>0.05), religion, (P>0.05) and their attitude towards the care of HIV/AIDS patients.Conclusions:The study suggested the need for more in-service trainings on HIV/AIDS for nurses to improve nurses’ knowledge and positive attitude towards the care of PLWHA.