Background During the last decade, French Guiana has been affected by major dengue fever outbreaks. Although this arbovirus has been a focus of many awareness campaigns, very little information is available about beliefs, attitudes and behaviors regarding vector-borne diseases among the population of French Guiana. During the first outbreak of the chikungunya virus, a quantitative survey was conducted among high school students to study experiences, practices and perceptions related to mosquito-borne diseases and to identify socio-demographic, cognitive and environmental factors that could be associated with the engagement in protective behaviors. Methodology/Principal Findings A cross-sectional survey was administered in May 2014, with a total of 1462 students interviewed. Classrooms were randomly selected using a two-stage selection procedure with cluster samples. A multiple correspondence analysis (MCA) associated with a hierarchical cluster analysis and with an ordinal logistic regression was performed. Chikungunya was less understood and perceived as a more dreadful disease than dengue fever. The analysis identified three groups of individual protection levels against mosquito-borne diseases: “low” (30%), “moderate” (42%) and “high” (28%)”. Protective health behaviors were found to be performed more frequently among students who were female, had a parent with a higher educational status, lived in an individual house, and had a better understanding of the disease. Conclusions/Significance This study allowed us to estimate the level of protective practices against vector-borne diseases among students after the emergence of a new arbovirus. These results revealed that the adoption of protective behaviors is a multi-factorial process that depends on both sociocultural and cognitive factors. These findings may help public health authorities to strengthen communication and outreach strategies, thereby increasing the adoption of protective health behaviors, particularly in high-risk populations. Author Summary Although dengue fever has been a focus of many awareness campaigns in Latin America, very little information is available about beliefs, attitudes and behaviors regarding vector-borne diseases among the population of French Guiana. At the initial onset of the first chikungunya outbreak, a quantitative survey was conducted among 1462 high school students aiming to study experiences, practices and perceptions related to mosquito-borne diseases and to identify factors that could be associated with protective behaviors. Chikungunya was less understood and perceived as a more dreadful disease than dengue fever. Students were clustered in three different groups according to their level of protection: “low” (30%), “moderate” (42%) and “high” (28%). Protective health behaviors were found to be performed more frequently among students who were female, lived with a parent who had a higher educational status, lived in an individual house, and had a better understanding of the disease. The results revealed that the adoption of protective behaviors is a multi-factorial process that depends on both socio-economic and cognitive factors. These findings may help the public health authorities to strengthen their communication and outreach strategy, thereby increasing the adoption of protective health behaviors, particularly in endemic countries and high-risk populations.