Following the 2005–2006 epidemic on Réunion Island, which affected 38.2% of the population, we used logistic regression to identify the determinants of Chikungunya virus (CHIKV) infection in a representative sample from the population seroprevalence survey. In a model adjusted for sex, age, the presence of a chronic disease, and the number of people living in the household, the independent variables significantly associated with a positive CHIKV serology were, in descending order of population attributable fraction: living in a single-family home with a garden (OR: 2.9; [95% CI 2.0–4.1], OR: 59.5%), a history of chikungunya among neighbors (OR: 2.7; [95% CI 1.7–4.2], OR: 43.8%), and not currently working or studying (OR: 1.9; [95% CI 1.4–2.5], OR: 41.5%), living at an altitude below 500 meters (<250 m, OR: 4.9; [95% CI 2.1–11.4]; 250–499 m, OR: 4.9; [95% CI 2.0–12.0], OR: 22.2%), body mass index (overweight, OR: 1.3; [95% CI 1.1–1.6]; obesity, OR: 1.6; [95% CI 1.1–2.4], p-value not calculated), and poor knowledge of CHIKV transmission (knowledge score of 0/4 correct answers, OR: 1.6; [95% CI: 1.1–2.3], p-value not calculated). The determinants of CHIKV infection are entomological, bioclimatic, and socioeconomic. These data should be taken into account for the control of future chikungunya epidemics. (R.A.)