Responses to COVID-19 public health interventions have been lukewarm. For example, only 64% of the US population has received at least two vaccinations. Because most public health interventions require people to behave in ways that are evolutionarily novel, evolutionary psychological theory and research on mismatch theory, the behavioral immune system, and individual differences can help us gain a better understanding of how people respond to public health information. Primary sources of threat information during the pandemic (particularly in early phases) were geographic differences in morbidity and mortality statistics. We argue that people are unlikely to respond to this type of evolutionarily novel information, particularly under conditions of high uncertainty. However, because individual differences affect threat perceptions, some individual differences will be associated with threat responses. We conducted two studies (during Phase 1 and 2 years later), using data from primarily public sources. We found that state-level COVID-19 morbidity and mortality rates had no relationship with mental health symptoms (an early indicator of how people were responding to the pandemic), suggesting that people-in general-were not attending to this type of information. This result is consistent with the evolutionary psychological explanation that statistical information is likely to have a weak effect on the behavioral immune system. We also found that individual differences (neuroticism, IQ, age, and political ideology) affected how people responded to COVID-19 threats, supporting a niche-picking explanation. We conclude with suggestions for future research and suggestions for improving interventions and promoting greater compliance.