Globally, human immunodeficiency syndrome (HIV) and its accompanying acquired immune deficiency syndrome (AIDS) have long been a public health threat due to the high death toll and the various effects on individuals and societies. Unfortunately, in developing countries such as Ghana, persons living with HIV/AIDS are victims of discrimination and rejection and are often excluded from social activities. Consequently, there is a need for mitigation strategies aimed at reducing the spread of the disease. Indeed, in human society, beliefs are fundamental to understanding people's intentions towards a given phenomenon. The purpose of this study was to assess students' perceived self‐efficacy, attitude towards and knowledge about HIV/AIDS. In this study, Bandura's self‐efficacy theory was used as a framework to assess the relationship between students' perceived self‐efficacy, attitude towards and knowledge about HIV/AIDS. A total of 342 students of at least 15 years old were recruited from junior and senior high schools and a public university to complete two scales: the general self‐efficacy and attitude and knowledge about HIV/AIDS scales. While there was a positive correlation among self‐efficacy, attitude and knowledge, attitude and knowledge combined to predict self‐efficacy. The limitations of the study, recommendations for future research and policy implications are discussed herein.