Introduction: Oral manifestations can be the first signs of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and a useful marker for the progression of this disease. The present study aimed to determine the prevalence of oral manifestations and examine their relationship with socio-demographic factors in HIV-positive patients in the health centers affiliated to Zahedan University of Medical Sciences (Southeast Iran). Methods: In this cross-sectional study in addition to determining oral manifestations based on the classification of EC-clearing house (European Commission clearing house), information such as age, gender, marital status, residence, education, occupation, habits, oral hygiene, loss of weight in the last six months. Body Mass Index (BMI), mode of HIV transmission, stage of disease, anti-retroviral therapy (ART), and duration of HIV were gathered through direct question from the patients or the information contained in their records. Then the relationship between various factors and oral manifestations was analyzed using Chi-square, Fisher’s Exact Test, Student T Test, Mann- Whitney tests and logistic regression. Results: Oral examination was performed on 119 HIV-positive patients who were 69.7% male and 30.3% female and had a mean age of 35.4±12.7 years. Oral manifestations were found in 57.1% of the patients. Pseudomembranous candidiasis (34.1%) and linear gingival erythema (33%) were the most common lesions in these patients. The probability of oral manifestations occurrence increased with age and duration of smoking in smokers with HIV (P=0.036 and P=0.012, respectively). Conclusion: Most oral manifestations were those strongly associated with HIV infection (91%). Timely diagnosis and treatment of oral manifestations in HIV patients should be considered in conjunction with other treatments.