The increased access to effective antiretroviral treatment (ART) has made HIV comparable to a chronic disease in terms of life expectancy. Needs related to sexuality and reproduction are central to overall health and well-being. An interpretative meta-synthesis was performed to synthesize and assess how HIV-positive women's experiences of sexuality and reproduction have been described in qualitative studies. A total of 18 peer-reviewed qualitative studies were included, which comprised a total of 588 HIV-positive interviewed women. The studies originated from resource-rich countries outside the Asian and African continents. The analysis, resulting in a lines-of-argument synthesis, shows that HIV infection was a burden in relation to sexuality and reproduction. The weight of the burden could be heavier or lighter. Conditions making the HIV burden heavier were: HIV as a barrier, feelings of fear and loss, whereas motherhood, spiritual beliefs, and supportive relationships made the HIV burden lighter. The findings are important in developing optimal health care by addressing conditions making the burden of HIV infection lighter to bear. In future research there is a need to focus not only on examining how HIV-positive women's sexual and relationships manifest themselves, but also on how health care professionals should provide adequate support to the women in relation to sexuality and reproduction.