Industrialized societies which continue to use fossil fuel energy sources are considering adoption of Carbon Capture and Storage (CCS) technology to meet carbon emission reduction targets. Deep geological storage of CO2 onshore faces opposition regarding potential health effects of CO2 leakage from storage sites. There is no experience of commercial scale CCS with which to verify predicted risks of engineered storage failure. Studying risk from natural CO2 seeps can guide assessment of potential health risks from leaking onshore CO2 stores. Italy and Sicily are regions of intense natural CO2 degassing from surface seeps. These seeps exhibit a variety of expressions, characteristics (e.g., temperature/flux), and location environments. Here we quantify historical fatalities from CO2 poisoning using a database of 286 natural CO2 seeps in Italy and Sicily. We find that risk of human death is strongly influenced by seep surface expression, local conditions (e.g., topography and wind speed), CO2 flux, and human behavior.