Abstract Background Psychological distress has increased remarkably, especially among younger age groups, during the last years. Both psychological distress and exposure to strenuous working conditions are known risk factors for sickness absence (SA). We examined whether psychological distress and working conditions are jointly associated with SA periods of 1-7 days and 8+ days among young and midlife Finnish employees. Methods We linked survey data from the Helsinki Health Study cohort from 2017 (response rate 51.5%) with the employer’s SA register for the City of Helsinki, Finland (82% consented to the linkage; n = 3949, 80% women, age 19-39 years). Mean follow-up time was 2.1 years. We calculated rate ratios (RR) and 95% confidence intervals (CI) for SA periods of 1-7 days and 8+ days using negative binomial regression models among participants with and without psychological distress, and with and without exposure to strenuous working conditions. Psychological distress was measured with the emotional wellbeing subscale of RAND-36 (cut-off 60 points). Working conditions included physical and mental strenuousness of work and hours per day spent in heavy physical work. Results Participants with psychological distress and exposure to strenuous working conditions had the highest age- and gender-adjusted RRs for SA periods of ≥ 8 days (physically strenuous work: RR: 2.38, CI: 1.97-2.88; mentally strenuous work: RR: 2.08, CI: 1.72-2.53; ≥3 h per day spent in physical work: RR: 2.48, CI: 2.01-3.06), the interactions being additive. The associations were weaker for SA periods of 1-7 days. Adjusting for marital and employment status, education, alcohol use, smoking and body mass index only slightly attenuated these associations. Conclusions Psychological distress and exposure to strenuous working conditions were additively associated with SA. Both individual- and workplace-related risk factors for SA are important to be considered when planning preventive actions. Key messages • Young and early midlife Finnish employees with simultaneous psychological distress and exposure to strenuous working conditions had the highest rates of SA periods, the interactions being additive. • Both psychological distress and exposure to strenuous physical and mental working conditions should be considered when planning preventive actions to reduce employees’ SA.