Background: Mental health problems are a leading cause of long-term sickness absence (LTSA). Workers at risk of mental LTSA should preferably be identified before they report sick. The objective of this study was to examine mental health symptoms as predictors of future mental LTSA in non-sicklisted workers. Methods: Prospective cohort study of 4877 non-sicklisted postal workers. Mental health symptoms were measured at baseline in November 2010 with the Four-Dimensional Symptom Questionnaire (distress and depressed mood) and Maslach's Burnout Inventory (fatigue). Mental health symptom scores were analyzed against incident mental LTSA retrieved from an occupational health register in 2011 and 2012. The area under the receiver operating characteristic curve (AUC) represented the ability of mental health symptom scores to discriminate between workers with and without mental LTSA during 2-year follow-up. Results: Complete cases analysis included 2782 (57 %) postal workers of whom 73 had mental LTSA during 2-year follow-up. Distress fairly (AUC = 0.75; 95 % CI 0.67-0.82) and both depressed mood (AUC = 0.64; 95 % CI 0.57-0.72) and fatigue (AUC = 0.61; 95 % CI 0.53-0.69) poorly discriminated between workers with and without mental LTSA during 2-year follow-up. The discriminative ability of distress did not improve by adding depressed mood and fatigue. Conclusions: Measurement of distress sufficed to identify non-sicklisted postal workers at risk of future mental LTSA. The Four-Dimensional Symptom Questionnaire distress scale is a promising tool to screen working populations for of mental LTSA, which enables secondary preventive strategies.