Chronic inflammation and poor mitochondrial function significantly contribute to the subjective feeling of fatigue upon waking, even after 8 or more hours of sleep.
Low-grade systemic inflammation elevates pro-inflammatory cytokines such as IL-6 and TNF-alpha, which are known to interfere with sleep regulation and reduce the restorative quality of sleep. These cytokines can disrupt normal sleep architecture, particularly deep (slow-wave) sleep, leading to unrefreshing rest despite adequate sleep duration.
Mitochondria are responsible for producing cellular energy in the form of ATP. When mitochondrial function is impaired—due to oxidative stress, aging, nutrient deficiencies, or chronic disease—cells in energy-demanding tissues like muscles and the brain struggle to recover overnight. This leads to persistent fatigue, muscle weakness, and cognitive sluggishness upon waking.
Both inflammation and mitochondrial dysfunction are tightly interlinked. Inflammation can damage mitochondria, and damaged mitochondria can release signals that promote further inflammation. This feedback loop contributes to systemic fatigue and poor sleep quality. Individuals with chronic conditions such as fibromyalgia, chronic fatigue syndrome, or long COVID often exhibit both features, which may explain their profound morning exhaustion.
Conclusion: Even when sleep duration is sufficient, chronic inflammation and poor mitochondrial health can undermine the body’s ability to recover and regenerate during sleep, resulting in morning exhaustion and reduced daytime functioning.