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Objectives To study the association between job demands and distress among working adults and to test whether perceived supervisor support moderates this relationship.Design Mixed-effects analysis of repeated measures from a population-based cohort study, estimating overall (combined within-person and between-person) associations.Setting The Netherlands Longitudinal Study on Hearing (NL-SH), an ongoing Dutch cohort with nationwide recruitment and follow-up including four measurement waves.Participants A total of 989 employed individuals (≥12 hours/week) with 1858 observations had complete data on distress, job demands, supervisor support and covariates.Primary and secondary outcome measures The dependent variable was distress, measured using the 16-item distress subscale (range 0–32) of the Four-Dimensional Symptom Questionnaire. Job demands and supervisor support were assessed with subscales from the Job Content Questionnaire. Multilevel linear models were used to estimate main and interaction effects, adjusted for age, sex, educational level, hearing impairment, contract type and chronic diseases.Results Higher job demands were associated with greater distress (B=0.22, 95% CI (0.17 to 0.27)). Higher supervisor support was associated with lower distress (B=–0.26, 95% CI (–0.38 to –0.15)). The interaction between job demands and supervisor support was statistically significant (B=-0.02, 95% CI (-0.04 to 0.001), p=0.042). Stratified analyses showed that the association between job demands and distress was stronger among employees with low supervisor support (B=0.27, p<0.001) than among those with high support (B=0.13, p=0.008).Conclusions Job demands and supervisor support were independently associated with distress. Supervisor support appeared to buffer the impact of job demands, as the association between job demands and distress was stronger among employees reporting low levels of supervisor support. These findings underscore the importance of strengthening supportive supervisor practices, alongside addressing excessive job demands, as integral components of workplace mental health strategies.