Background <p>Epidemiological studies show associations between chronic noise exposure and disease, but the biological pathways remain poorly understood. In this explorative pilot study, we investigate the mechanisms that may link sleep disruption by environmental noise with disease, and the efficacy of a non-pharmacological intervention to mitigate these effects.</p> Methods <p>We conducted a cross-over trial (ClinicalTrials.gov: NCT05319262; 2022-03-09) where N = 12 healthy individuals slept for five consecutive nights in acoustically isolated bedrooms. Nights included one familiarisation night; one quiet baseline night; one night with road, rail and air traffic noise of levels 45-65 dB <i>L</i>_AS,max; one night with continuous 45 dB broadband pink noise; and one night with both traffic noise and pink noise. Sleep was measured with polysomnography. Perceived sleep quality and recouperation were measured with morning questionnaires. Daily blood samples were collected for metabolomics analysis.</p> Results <p>Here we show that discrete traffic noise events induced acute elevations of the odds ratio product, indicating acute sleep fragmentation, even while total sleep time and overall sleep macrostructure were preserved. Traffic noise is further associated with significant elevations in concentrations of leucine, lactic acid, and acetone relative to quiet control. Sleep and metabolic disturbances by traffic noise are attenuated when pink noise is played continuously throughout the night.</p> Conclusions <p>Noise-induced sleep fragmentation is followed by changes in metabolic processes that in the long-term may be precursors for cardiometabolic disorders. Masking of traffic noise by continuous, neutral sound may mitigate acute physiological sleep disturbance and downstream metabolic effects. These results should be interpreted cautiously, given the limited sample size and subject homogeneity.</p>