Background: The exposome encompasses all factors people encounter through life, with the skin constantly exposed. While particulate matter (PM) and sleep deprivation are known to contribute to barrier dysfunction, their combined effects remain unclear. Objective: To evaluate the independent and combined effects of PM exposure and short-term sleep deprivation on skin barrier function. Methods: Forty healthy Korean women (aged 24–58 years) were enrolled in this study. Forearms were divided into 4 sites: control, PM exposure, sleep deprivation, and PM plus sleep deprivation. Parameters such as trans-epidermal water loss (TEWL), hydration, elasticity, roughness, and redness were measured at baseline and post-exposure. RNA sequencing and reverse transcription-polymerase chain reaction were conducted on tape-stripped skin samples. Results: PM exposure significantly increased TEWL (+25.59%, p<0.01), roughness (+21.9%, p<0.01), and redness (+13.7%, p<0.0001) while reducing elasticity (−3.98%, p<0.01). Sleep deprivation modestly reduced elasticity (−1.39%, p<0.05) without affecting other parameters.Combined PM and sleep deprivation did not further exacerbate barrier dysfunction compared to PM alone. RNA sequencing revealed reduced FLG and LORICRIN expression and upregulated endoplasmic reticulum (ER) stress markers (HSP90B1, CANX) in both PM and sleep deprivation conditions. Conclusion PM exposure impaired skin barrier function, while short-term sleep deprivation alone did not significantly affect the barrier, either independently or in combination with PM.However, it was observed that the sleep deprivation-only, while not directly causing barrier damage, induced changes in ER stress-related gene expression in tape-stripped skin samples, like the PM exposure-only. This suggests that such signaling pathways could potentially exacerbate skin barrier deterioration.