Risk epidemic and complexity are linked by space and interactions. First, space matters in risk situations because of its ability to hold concurrently and simultaneously favorable conditions for a future emergence or re-emergence of epidemics. Second, space matters as a mediator of interactions, social as environmental, and at different levels. Risk is dynamic and its spatio-temporal dimension increases difficulties to catch it. Empirical data lack off precision to follow epidemiological outbreak. Complex system theory and connected methodologies can help us to enlighten this empirical failure. First, we present some knowledge about risk, health and complexity. Second we present social and spatial data based on the first epidemic of cholera in the city of Rouen, in 1832. Third we propose two models to explore the diffusion of this epidemic.