Background Fatigue following acute viral illnesses is a major issue that complicates the clinical course of several epidemic and non-epidemic viral infections. There is a noticeably higher trend of patients with symptoms that persist after initial recovery from acute COVID-19. This study seeks to obtain more data about the prevalence of post-COVID-19 fatigue and the factors associated with higher fatigue frequency among patients who had COVID-19. Methods A single center cross-sectional study was performed between May 2021 and January 2022 at University Health, Kansas City, Missouri, USA. The Fatigue Assessment Scale (FAS) was utilized to measure post-COVID-19 fatigue. Descriptive and comparative statistics were used to describe clinical and sociodemographic features of patients. Analysis of variance (ANOVA), the chi-square test, and Fisher’s exact test were used to examine the statistical association between the FAS score and other clinical and sociodemographic factors. Results One hundred and fifty-seven patients who had been diagnosed with COVID-19 and diagnosed at University Health were enrolled in our study. Overall, 72% of patients ( n = 113) were female. The mean ± standard deviation of the FAS score was 21.2 ± 9.0. The prevalence of post-COVID-19 fatigue among our studied sample was 43.3%. The findings of this study suggest that female patients have a significantly higher fatigue score compared with male patients ( P < 0.05). Conclusions Post-COVID-19 fatigue is a major issue following the initial acute illness with COVID-19, with a prevalence of 43.3%. We recommend implementing standardized measures to screen for post-COVID-19 fatigue, especially among female patients. Supplementary Information The online version contains supplementary material available at 10.1007/s11845-022-03011-z.

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