The Orbiel Valley lies downstream from the former Salsigne gold mine complex (Aude department, Occitanie). The Salsigne mine and its associated sites are located in a mountainous area at the southern tip of the Massif Central, about 20 kilometers north of Carcassonne. They were mined from ancient times until 2004. Nearly 12 million tons of ore were processed at the site to extract primarily gold but also arsenic, with the unprocessed ore remaining on-site, notably in the form of tailings. Starting in 1999, part of the mining complex underwent remediation work. The health impact of this former mining complex has been a recurring concern among the population since the late 1990s, particularly following the floods of 1996. These concerns have led to the conduct of several health studies over the past 20 years. In October 2018, new floods occurred in the valley and carried contaminated sediments downstream. In this context, the Occitanie Regional Health Agency (ARS) consulted Santé publique France on the “appropriateness of proposing new epidemiological studies or updating those already conducted.” In its response, Santé publique France proposed consulting with stakeholders in the valley to assess the relevance of conducting a new health study. The decision was made to focus on a study of mortality from cancers, circulatory system diseases, and Parkinson’s disease. The objectives of the study were: (i) to describe the mortality observed among the population residing in the municipalities of the Orbiel Valley and potentially exposed to mining pollution; and (ii) to assess whether this observed mortality differed from that of a population not exposed to mining pollution. The causes of death considered potentially linked to metal exposure were cancers (all cancers, pharynx, lung, digestive organs, prostate, kidney, urothelial, lymphoid, hematopoietic, and related cancers, carcinoma), circulatory system diseases, and neurodegenerative diseases such as Parkinson’s disease. The analyses covered the period 2004–2017, based on the underlying cause of death, for all genders combined and by gender when sample sizes were sufficient. Age- and sex-standardized mortality rates were calculated by cause of death using the department as the reference population, in order to compare mortality in the area considered exposed (20 municipalities in the valley) and a non-exposed area (62 municipalities located within a radius of approximately 15 km around the exposed area). The analysis of the difference in mortality between the two areas was conducted by accounting for potential confounding factors (social deprivation index, degree of rurality of the municipalities, index of access to a general practitioner, vineyard area, presence of radon) using negative binomial regression. The results show no observable difference in mortality for the diseases studied between the exposed and unexposed areas, whether for all genders combined, among men, or among women. This study nevertheless has limitations related primarily to the size of the population and the analysis conducted at the municipal level rather than the individual level (an approach that may lead to ecological biases). It should be noted, however, that the absence of statistically significant excess mortality does not mean that pollution management measures around former sites are unnecessary. Environmental data are essential for characterizing environmental pollution and must continue to guide management measures aimed at protecting public health.