Sleep is a cardinal biological process that backstops central nervous system function, which also plays a crucial role in regulating systemic homeostasis, including immune activities. Cytokines, particularly interleukin-1β and tumor necrosis factor-α, act as mediators bridging sleep and inflammation, also influencing both sleep architecture and sleep–wake cycle. Sleep deprivation and sleep disorders such as insomnia, narcolepsy, hypersomnia, or obstructive sleep apnoea may disrupt cytokine production, alter their circadian rhythm of release, and shift secretion peaks from night to day. These changes contribute to daytime fatigue, impaired cognitive and physical performance, increased susceptibility to infections and/or systemic inflammation. Molecular studies indicate that insufficient sleep primes immune cells to enhance pro-inflammatory responses, creating a feedback loop with neuroendocrine pathways that further exacerbates sleep patterns and inflammatory dysregulation. Understanding the bidirectional relationship between sleep and cytokines may highlight the role of sleep as an active component of immunity regulation and underscore the potential usefulness of multilevel interventions that include complementary and integrative health approaches restoring sleep, normalizing cytokine rhythms and mitigating inflammation.