The COVID-19 pandemic has had a disastrous impact on the global economic and social fabric. Zoonotic disease spill-over from other species has become a familiar phenomenon, and the need for a more proactive approach to minimise exposure to and opportunities for spill-over is widely recognised. In particular, it is crucial to incorporate measures to combat illegal wildlife trade (IWT) in cross-sectoral policies addressing the triple challenges of human health, biodiversity loss and the climate crisis. Implementing an integrated One Health approach is estimated to cost one-hundredth of the economic damage that pandemics produce. This policy brief recommends incorporating the combatting of IWT into a much wider-ranging, multi-sectoral One Health approach for Africa.