Long COVID fatigue represents a complex and multifaceted condition that remains poorly understood despite substantial research efforts. This chapter presents a comprehensive examination of fatigue in the context of post-COVID-19 syndrome, focusing on three key areas: the fundamental definition of fatigue, the crucial distinction between fatigue and fatigability, and a comparative analysis with other post-viral syndromes. The chapter introduces a conceptual framework that defines Long COVID fatigue as decreased physical and/or mental performance resulting from COVID-19-induced changes in central, psychological, and peripheral factors. A significant emphasis is placed on understanding the distinction between fatigue and fatigability, with recent research demonstrating that perceived fatigability is more prevalent than objective fatigability in post-COVID-19 patients. The chapter also provides a detailed comparison of Long COVID fatigue with other post-viral syndromes, including post-SARS, post-EBV, and ME/CFS, highlighting distinctive features in onset patterns, symptom manifestation, disease trajectory, and recovery characteristics. This comparative analysis reveals Long COVID’s unique characteristics, including its variable onset, broad multi-system involvement, and heterogeneous recovery patterns. The chapter concludes by emphasizing the need for individualized treatment approaches that acknowledge the condition’s distinctive pathophysiology and complex presentation. This understanding sets the foundation for future research directions aimed at developing more targeted and effective therapeutic strategies.