Multiple social interventions were introduced to contain the COVID-19 pandemic across Africa, limiting social engagement, school and workplace attendance, and travel. In anticipation of negative economic consequences and social impact, many governments introduced cash transfers, social pensions, food aid, and utility and tax waivers. However, people living precariously and/or under conditions of structural vulnerability were often unable to access to this support. A rapid review was undertaken on COVID-19 and the effects of interventions on human rights in African countries, examining primary studies, editorial notes, opinion papers, and literature reviews, with focus on qualitative approaches and discussions. In examining the links between health, human rights and non-pharmaceutical interventions on vulnerable populations, the review identified that: (1) people who were vulnerable were excluded from or not adequately represented in policy responses to COVID-19; (2) the precarious socio-economic conditions of these populations were not adequately addressed by dominant policy responses; and (3) only partial support was offered to those whose relationship with the state was ambiguous or conditional, so compromising human rights. Interactions between health, human rights, and underlying social and economic conditions amplified poor health and impoverishment of those who were already vulnerable. The challenge is to find a balance between stopping the spread of COVID-19 and the protection of human rights; to implement population-specific responses to supplement uniform public health responses; and to address causes (structural vulnerability) rather than symptoms. There is a need to plan rather than react to pandemics, and to co-construct interventions with rather than delivering instructions to populations. These recommendations serve as instruments to be considered when designing new policies, to incorporate a human rights perspective in responses to current and future pandemics.