Mathematical modelling has played an increasingly prominent role in public health responses, for example by offering estimates of how infectious disease incidence over time may be affected by the adoption of certain policies and interventions. In this paper, we call for greater research and reflection into the ethics of mathematical modeling in public health. First, we present some promising ways of framing the ethics of mathematical modeling that have been offered in the very few publications specifically devoted to this subject. Second, to draw out some issues that have not yet been sufficiently considered, we bring in the case of mathematical modeling in voluntary medical male circumcision (VMMC) initiatives for HIV prevention in Africa. We argue that greater attention should be paid to ethical considerations in mathematical modeling, particularly as its use is becoming more widespread and its potential impacts are becoming greater in the ‘big data’ era, as witnessed during the COVID-19 pandemic.