BackgroundSubstance use is more prevalent among unemployed subjects compared to employed ones. However, quantifying the risk subsequent of job loss at short-term according to substance use remains underexplored as well as examining if this association persist across various sociodemographic and occupational positions previously linked to job loss. We examined this issue prospectively for alcohol, tobacco, cannabis use and their combination, among a large population-based sample of men and women, while taking into account age, gender, overall health status and depressive symptoms.MethodsFrom the French population-based CONSTANCES cohort, 18,879 working participants were included between 2012 and 2016. At baseline, alcohol use disorder risk according to the Alcohol Use Disorders Identification Test (mild, dangerous, problematic or dependence), tobacco (non-smoker, former smoker, 1–9, 10–19, >19 cigarettes/day) and cannabis use (never, not in past year, less than once a month, once a month or more) were assessed. Employment status at one-year (working versus not working) was the dependent variable. Logistic regressions provided Odds Ratios(OR(95%CI)) of job loss at one-year, adjusting for age, gender, self-reported health and depressive state (measured with the Center of Epidemiologic Studies Depression scale). Stratified analyses were performed for education, occupational grade, household income, job stress (measured with the Effort-Reward Imbalance), type of job contract, type of work time and history of unemployment. In sensitivity analyses, employment status over a three-year follow-up was used as dependent variable.ResultsAlcohol, tobacco and cannabis use were associated with job loss, from the second to the highest category: 1.46(95%CI:1.23–1.73) to 1.92(95%CI:1.34–2.75), 1.26(95%CI:1.09–1.46) to 1.78(95%CI:1.26–2.54) and 1.45(95%CI:1.27–1.66) to 2.68(95%CI:2.10–3.42), respectively, and with dose-dependent relationships (all p for trend <0.001). When introduced simultaneously, associations remained significant for the three substances without any between-substance interactions. Associations remained significant across almost all stratifications and over a three-year follow-up as well as after adjustment for all the sociodemographic and occupational factors.ConclusionsAlcohol, tobacco and cannabis use were independently associated with job loss at short-term, with dose-dependent relationships. This knowledge will help refining information and prevention strategies. Importantly, even moderate levels of alcohol, tobacco or cannabis use are associated with job loss at short-term and all sociodemographic and occupational positions are potentially concerned.