The SARS-CoV-2 outbreak and its impact on countries across the globe has been unprecedented. The lack of pharmaceutical interventions to prevent or treat infection have left States with limited avenues to control the spread of the virus. Many countries have introduced stringent lockdowns along with regulatory regimes that give governments new powers to compel compliance with these regulations and to punish non-compliance. This article investigates the use of compelled public health interventions during both the HIV and COVID-19 pandemics and how these can be aligned to human rights. This includes discussion on the use of interventions such as mandatory quarantine and isolation, compelled testing, criminalisation of HIV and SARS-CoV-2 transmission in Africa. This article also outlines what State obligations are in relation to pandemic responses, both in terms of mandating an effective response and which human rights principles should underscore these responses.Using South Africa as a case study, this article analyses whether the use of these interventions complies with international human rights law. We assess the use of compelled public health interventions in both the HIV and COVID-19 pandemics against established human rights principles applicable to pandemic responses. This article discusses lessons to be learnt about the relationship between human rights and public health interventions across both pandemics so as to guide human rights-based approaches to future pandemics as well as subsequent stages of the SARS-CoV-2 pandemic.