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Post-COVID-19 Condition (PCC) is a prevalent, persistent and debilitating phenomenon occurring three or more months after resolution of acute COVID-19 infection. Fatigue and depressive symptoms are commonly reported in PCC. We aimed to further characterize PCC by assessing the relationship between fatigue and depressive symptom severity in adults with PCC. A post hoc analysis was conducted on data retrieved from a randomized, double-blinded, placebo-controlled study evaluating vortioxetine for cognitive deficits in persons with PCC. We sought to determine the relationship between baseline fatigue [i.e. Fatigue Severity Scale (FSS) total score] and baseline depressive symptom severity [i.e. 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16) total score] in adults with PCC. The statistical analysis included baseline data from 142 participants. After adjusting for age, sex, education, employment status, history of major depressive disorder (MDD) diagnosis, self-reported physical activity, history of documented acute SARS-CoV-2 infection and body mass index (BMI), baseline FSS was significantly correlated with baseline QIDS-SR-16 (β = 0.825, p =.001) In our sample, baseline measures of fatigue and depressive symptoms are correlated in persons living with PCC. Individuals presenting with PCC and fatigue should be screened for the presence and severity of depressive symptoms. Guideline-concordant care should be prescribed for individuals experiencing clinically significant depressive symptoms. Fatigue and depressive symptom severity scores were not pre-specified as primary objectives of the study. Multiple confounding factors (i.e. disturbance in sleep, anthropometrics and cognitive impairment) were not collected nor adjusted for in the analysis herein. Unrestricted Research Grant from H. Lundbeck A/S, Copenhagen, Denmark. ClinicalTrials.gov Identifier: NCT05047952 [ABSTRACT FROM AUTHOR]