Big Events are periods during which abnormal large-scale events like war, economic collapse, revolts, or pandemics disrupt daily life and expectations about the future. They can lead to rapid change in health-related norms, beliefs, social networks and behavioural practices. The world is undergoing such Big Events through the interaction of COVID-19, a large economic downturn, massive social unrest in many countries, and ever-worsening effects of global climate change. Previous research, mainly on HIV/AIDS, suggests that the health effects of Big Events can be profound, but are contingent: Sometimes Big Events led to enormous outbreaks of HIV and associated diseases and conditions such as injection drug use, sex trading, and tuberculosis, but in other circumstances, Big Events did not do so. This paper discusses and presents hypotheses about pathways through which the current Big Events might lead to better or worse short and long term outcomes for various health conditions and diseases; considers how pre-existing societal conditions and changing 'pathway' variables can influence the impact of Big Events; discusses how to measure these pathways; and suggests ways in which research and surveillance might be conducted to improve human capacity to prevent or mitigate the effects of Big Events on human health.