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Introduction This study investigates the relationship between telework and mental health, focusing on mediating factors.Methods A sample was drawn from the June 2023 wave of the BELHEALTH study, which monitors mental health trends in Belgium. The sample included 2323 employed participants aged 18–64 years. Interventional effects mediation analyses were conducted to explore the relationship between the frequency of telework (monthly, weekly, and daily) and mental health outcomes including anxiety (Generalised Anxiety Disorder-7, binary), depression (Patient Health Questionnaire-9, binary), burnout (Burnout Assessment Tool-12, scale 1–5) and work engagement (Utrecht Work Engagement Scale-3, scale 1–5) through the following mediators: workload, emotional load, role conflict, autonomy, social support and skills use.Results Telework had both direct and indirect effects on mental health. The total effect of weekly telework on work engagement was —0.1614 (95% CI −0.2286 to –0.0972; p<0.01), indicating an overall decrease in work engagement when considering indirect and direct effects. While weekly telework was not significantly associated with anxiety and depression, it was directly associated with an average increase in burnout (0.1339, 95% CI 0.0875 to 0.1801; p<0.01), and a direct decrease in average work engagement (−0.2158, 95% CI −0.2783 to −0.1505; p<0.01). Indirectly, weekly telework was linked with burnout through various job demands and resources. For example, emotional load (−0.0427, 95% CI −0.0600 to –0.0272, p<0.01), and role conflict (−0.0266, 95% CI −0.0419 to −0.0122, p<0.05) were significant mediators of burnout.Conclusions It is essential to consider the job characteristics of employees who telework, and the resources they have available to foster healthy workplaces.