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Stigmatization of and discrimination against People Living with the Human Immunodeficiency Virus (PLHIV) and Acquired Immunodeficiency Syndrome (AIDS) are increasingly recognized as the single greatest challenge to slowing the spread of HIV and partly the cause of the increased death rate particularly in Africa and Ghana to be specific. The purpose of the study was to identify the causes and effects of stigmatization of and discrimination against PLHIV visiting the Central Regional Hospital of Ghana for treatment and care. The research was conducted with a sample size of 120. Purposive and convenient/accidental sampling techniques were used to select respondents for the study. The study revealed that some people in Ghana stigmatize PLHIV because of the misconceptions they have about the modes of HIV transmission, the myths surrounding HIV and AIDS as well as their socio-cultural backgrounds and orientations. These stigmatizing behaviors towards PLHIV have serious health, social and psychological effects on them in particular and the society at large. Based on the results of the study, it is recommended that there should be an intensification of education on HIV and AIDS through the media. This would make the population in Ghana more knowledgeable about the disease, which may help to reduce stigmatization of and discrimination against persons living with HIV.