Young women from Sub-Saharan Africa are at substantial risk of HIV acquisition. Data from UNAIDS suggests that 59% of new HIV infections in 2019 occurred in this population. Despite advances in HIV prevention and care, they remain at substantial risk making them a key population for control. In the present study we discuss the factors that put women from Sub-Saharan Africa at differential risk of HIV acquisition, and the possible impacts of the COVID-19 pandemic on HIV care and prevention on this population. The COVID-19 pandemic has brought unprecedented challenges for healthcare delivery, including HIV care, treatment and prevention. The indirect long-term effects of the pandemic may increase the vulnerability of young women to HIV infection. Statistical modelling studies predict increased HIV related deaths in excess of 500 000 in the next four years if services for testing and treatment are disrupted. Innovative ways of delivering prevention messages, HIV care, treatment and reducing new infections during and beyond the COVID-19 pandemic are warranted to protect young women from Sub-Saharan Africa.