Background: The SARS-CoV-2 pandemic has led most countries to take restrictive measures affecting social activities and individual freedoms to limit viral transmission. It was shown that practical, motivational and social barriers impact on adherence to the isolation and social distancing measures advocated by the health authorities. The purpose of this study was to develop and validate a COVID-19 Knowledges and Behavior Questionnaire adapted to a teenager and adult French population. Methods: CoVQuest-CC was developed by a multidisciplinary team made of infectious diseases physicians, medical virologist, specialists of infectious control, experts of the questionnaires methodology, experts in public health and prevention, and statisticians. CoVQuest-CC was responded to by a big cohort from the general population during their participation in a massive SARS-CoV-2 screening campaign in 2021 in Saint-Etienne, France. Results: The confirmatory factorial analysis yielded good results (CFI = 0.94, TLI = 0.94, RMSEA = 0.04), and confirmed the five-dimensional structure of the questionnaire. Each dimension had a satisfying internal consistency, with Cronbach alphas of 0.83, 0.71, 0.65, 0.72 and 0.83 for transmission knowledge, barrier gesture respect, tests acceptability, home isolation possibility and test practicability, respectively. Conclusions: According to our knowledge, CoVQuest-CC is the first validated, consistent and reliable self-administrated French-specific questionnaire investigating the general population’s knowledge and attitudes towards COVID-19. It shows acceptable psychometric properties and can be use by Public Health teams or caregivers for public health and research purposes. Trial Registration: The study protocol was approved by the IRB ILE-DE-FRANCE 1 (No. IRB: I ORG0009918). All participants were given written and verbal information about the study and gave informed consent to participate. ClinicalTrials.gov identifier (NCT number): NCT04859023.