Background: Transportation noise seems to impair self-reported health status (SRHS). However, only a few studies have considered the role of noise annoyance and noise sensitivity in this deleterious effect. This study aims investigating mediator and moderator roles of noise annoyance and noise sensitivity. Methods: The DEBATS longitudinal study included in 2013, 1,244 participants aged over 18 years and living around three French airports. These participants were followed up in 2015 and 2017. They self-reported their perceived health status, aircraft noise annoyance, and their noise sensitivity via a questionnaire during the three visits. Noise maps were used to estimate aircraft noise levels at the facade of participants' residence. Generalized linear mixed models with a random intercept at the participant level were used. Results: Aircraft noise levels were associated with severe annoyance. Severe annoyance tent to be associated, with impaired SRHS. Aircraft noise levels were associated with impaired SHRS only in men (OR = 1.47, 95% CI = (1.02, 2.11), for a 10-dBA Lden increase in aircraft noise levels) with a weaker association adjusted for annoyance (OR = 1.36, 95% CI = (0.94, 1.98)). The association was stronger in men who reported high noise sensitivity (OR = 1.84, 95% CI = (0.92, 3.70), versus OR = 1.39, 95% CI = (0.90, 2.14), for men who were not highly sensitive to noise). Conclusion: From our results, the deleterious effect of aircraft noise on SRHS could be mediated by noise annoyance and moderated by noise sensitivity. Further studies using causal inference methods are needed for identifying causal effect of exposure, mediator and moderator.