The key finding
A 2025 narrative review of 50 studies found that chronic sleep deprivation consistently reduces melatonin production, and these lower melatonin levels are associated with measurable immune changes: elevated inflammatory markers (such as IL-6 and TNF-α), increased oxidative stress, and reduced activity of key immune cells including natural killer (NK) cells and CD4+ lymphocytes. The review, spanning research from 2000 to 2025, shows a recurring pattern where disrupted circadian rhythms suppress melatonin and correlate with immune imbalance across diverse study designs.
What the study looked like
This was a narrative review analyzing 50 published studies rather than a single experiment. The research team examined diverse study types—observational cohort studies, experimental sleep deprivation trials, and mechanistic laboratory work—all investigating the relationship between sleep loss, melatonin levels, and immune function. The included studies spanned 25 years and focused on various populations: healthy adults undergoing controlled sleep restriction, older adults with naturally lower melatonin, shift workers experiencing chronic circadian disruption, and patients with infectious diseases like COVID-19. Researchers looked at biomarkers including melatonin concentrations, inflammatory cytokine levels, immune cell counts and activity, oxidative stress markers, and measures of gut barrier integrity. The heterogeneity of methods across studies allowed the authors to identify consistent patterns despite differences in measurement techniques and participant characteristics.
Why researchers think this happened
Melatonin appears to function as both a sleep regulator and an immune modulator, creating a biological bridge between rest and defense systems. The hormone influences multiple immune pathways, particularly the NF-κB signaling cascade that controls inflammatory responses. When sleep deprivation suppresses melatonin synthesis, this regulatory brake on inflammation weakens. The review’s authors note that melatonin also supports mitochondrial function in immune cells—the energy factories these cells need to mount effective responses—and helps maintain the integrity of the gut barrier, where much of the immune system operates. These mechanisms align with prior research showing melatonin receptors on various immune cell types. The pattern is especially pronounced in vulnerable groups: older adults naturally produce less melatonin, while shift workers face repeated circadian disruption. Experimental work on SARS-CoV-2 infection suggested melatonin may influence both viral entry mechanisms and inflammatory control, though the review emphasizes these findings require further validation.
How to read this carefully
As a narrative review rather than a systematic meta-analysis, this synthesis relied on the authors’ selection of studies rather than exhaustive search protocols, which introduces potential publication bias. The heterogeneity of methodologies across the 50 included studies makes direct comparisons challenging—different labs measured melatonin and immune markers using varying techniques, timescales, and populations. Critically, the demonstrated relationship is correlational: lower melatonin levels occur alongside immune changes, but the review cannot definitively prove melatonin reduction causes immune dysfunction rather than both being effects of sleep loss. Many studies were observational or short-term experimental designs rather than long-term randomized controlled trials. The therapeutic findings regarding melatonin supplementation come primarily from animal models and small human studies, not large clinical trials with standardized dosing protocols.
What this means for everyday life
This research reinforces that sleep affects more than just alertness—it may influence how your body handles infections and inflammation. For people with irregular sleep schedules, whether from shift work, caregiving, or personal habits, the connection between rest and immune function might be worth considering when thinking about overall health strategies. While the review mentions melatonin supplementation, the evidence doesn’t yet support specific dosing recommendations for immune support in healthy populations, and you shouldn’t view melatonin as a substitute for adequate sleep. The more actionable insight is prioritizing consistent sleep schedules when possible, given the circadian system’s role in melatonin production. For older adults experiencing both declining melatonin and increased infection susceptibility, understanding this link may inform conversations with healthcare providers about sleep quality as part of preventive care, though more research is needed before clear clinical guidelines emerge.