Fatigue and depression are highly comorbid phenotypes with partially overlapping symptoms. The main aims of the present study are to: (i) identify the risk of current fatigue and depression; (ii) determine if the depression symptoms experienced by individuals who are fatigued (N=766) and non-fatigued (N=1849) are different; and (iii) identify if the fatigue symptoms experienced by depressed (N=275) and non-depressed (N=2340) individuals are different, in a community-based sample of Australian twins aged over 50years.Fatigue and depression symptom profiles and classifications were generated using the Schedule of Fatigue and Anergia (SOFA); the General Health Questionnaire; and the Delusions-Symptoms-States Inventory, States of Anxiety and Depression questionnaires. The association between co-occurring fatigue and depression was assessed using prevalence ratios. Differences in the preponderance of fatigue and depression symptoms were assessed using logistic regression modeling.Individuals with either fatigue or depression have an approximately two-fold increased risk for comorbid presentation of both traits, compared to the general population. Logistic regression analysis indicated that fatigued individuals were significantly more likely to report all of the Diagnostic and Statistical Manual of Mental Disorders (DSM) depression symptoms assessed in the study. Similarly, depressed individuals were significantly more likely to report all SOFA fatigue symptoms.Fatigue and depression are highly correlated traits within the community. Depression symptomatology and prevalence are significantly increased in fatigued individuals. Fatigue and especially the symptoms of insomnia and poor concentration are strong predictors of depression. Notably, the association between fatigue and depression is independent of their overlapping symptomatology. Therefore, presentation with fatigue, and in particular the symptoms of insomnia and poor concentration, should be considered as warning signs of depression in older adults.