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Abstract Background and Aims Acquired immune deficiency syndrome (AIDS) are a chronic and disabling disease that has a significant impact on quality of life due to weakening of physical health, financial problems and social stigma. This study aims to validate the Health‐related quality of life (HRQOL) model in people with human immunodeficiency viruses (HIV) in Iran. Methods Four hundred and fifty‐two people with HIV from Imam Khomeini Hospital between the age of 18 and 65 years (men: 308, women: 144) participated in the research. anonymously completed a battery of questionnaires, namely the Persian basic psychological need satisfaction and frustration scale, SF‐36, PSQI and mindful attention awareness scale. The method of the present study was the structural equation model. Results Current findings indicated there is a significant positive between mindfulness and need satisfaction, physical and mental health and, significant negative between mindfulness and quality and quantity of sleep. Mindfulness and need satisfaction are significant positive predictors of quality of life in people with HIV. Quality and quantity of sleep are significant negative predictors of quality of life in people with HIV. There is a positive significance between need satisfaction and physical and mental health but there is a negative significance between need satisfaction and quality and quantity. there is a negative significant between the quality and quantity of sleep with physical and mental health. Mindfulness facilitates the satisfaction of more psychological needs and improves the quality of sleep. The quality of sleep is a negative significant predictor for physical and mental health but the quantity of sleep is a negative significant predictor for physical health. Conclusion The HRQOL model can explain 18% of physical health and 16% of mental health in people with HIV in Iran. The elements of this model can be useful in evaluating and treating people with HIV in the Iranian Population. They also can use the models to plan for better services.