PURPOSE: Population-based and clinical studies suggest that higher cardiorespiratory fitness (CRF) is associated with better mental health and less sleep complaints. However, in these studies mental health and sleep are assessed through questionnaires. The increased use of sedatives and hypnotics coupled with their known adverse health associations raises potential public health concerns. So far no studies have assessed if CRF is associated with incident use of sedative-hypnotics in the general population. METHODS: This prospective study included 30,481 participants (52.2% women, mean age 51.0 years) from the third survey of the Norwegian Nord-Trøndelag Health Study in 2006-08. Data on psychotropic drugs were retrieved from the Norwegian Prescription Database and incident sedative-hypnotics was measured as first registered prescription with code N05C in the Anatomical Therapeutic Chemical Classification System. Participants using any psychotropic drugs three months prior to participation and three months after participation were excluded. The participants were followed from three months after participation until incident use of sedative-hypnotics, emigration, death or study end 1st of January 2018. Baseline CRF (ml/kg/min) was determined using non-exercise algorithms based on sex, age, waist circumference, physical activity, and resting heart rate (eCRF). Baseline eCRF was further grouped into age- and sex-specific tertiles. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between baseline eCRF and incident use of sedative-hypnotics. The multivariable analyses were adjusted for age, sex, education, symptoms of anxiety and depression, limiting-longstanding illness, and sleep problems. RESULTS: During follow-up, 4,632 (15.2 %) of the participants used sedative-hypnotics. In fully adjusted models comparing with the lowest tertile of eCRF, those in the middle and upper eCRF tertiles had 8% (HR: 0.92, 95% CI: 0.84-1.00) and 24% (HR: 0.86, 95% CI: 0.77, 0.62-0.94) lower risk of incident use of sedative-hypnotics. CONCLUSION: Higher CRF is associated with less prescribed sedative-hypnotics in the general population. This effect seems to be more pronounced for those with highest CRF. Characters no space (max 2000): 1967.