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Mental health and emotional disorders are often associated with higher mortality risk. Whether higher cardiorespiratory fitness (CRF) reduces the risk for all-cause mortality in individuals with emotional distress is not well known.Participants were 5240 men (mean age 46.5±9.5 years) with emotional distress (including depression, anxiety, thoughts of suicide, or a history of psychiatric or psychological counseling) who completed an extensive medical examination between 1987 and 2002, and were followed for all-cause mortality through December 31, 2003. Cardiorespiratory fitness was quantified as maximal treadmill exercise test duration and was grouped for analysis as low, moderate, and high. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs.During a median of 8.7 years (range, 1.0-16.9 years) and 46,217 person-years of follow-up, there were 128 deaths from any cause. Age- and examination year–adjusted all-cause mortality rates per 10,000 person-years according to low, moderate, and high CRF groups were 64.7 (95% CI, 44.9-89.3), 28.0 (95% CI, 23.8-31.5), and 19.6 (95% CI, 17.1-21.6) (trend P<.001) in men who reported any emotional distress. Overall, the multivariable-adjusted HRs and 95% CIs across incremental CRF categories were 1.00 (referent), 0.54 (0.32-0.90), and 0.47 (0.26-0.85), linear trend P =.03.Among men with emotional distress, higher CRF is associated with lower risk of dying, independent of other clinical mortality predictors. Our findings underscore the importance of promoting physical activity to maintain a healthful level of CRF in individuals with emotional distress.