Sleeping microenvironment (SME), is characterized by higher temperature, humidity, and CO2 concentration. Emission of Volatile Organic Compounds (VOC) in SME is important considering the long duration people spend there with high proximity between their respiration inlets and potential emission sources, such as bedding material. This study concentrates on the influence of SME conditions on VOC emissions from polyurethane mattresses, and provides first approximation for inhalation exposure during sleep, based on measured emissions. Eight types of polyurethane mattresses were tested in a parallel continues-flow chamber system, to compare between VOC emission under different temperature, relative humidity, and CO2 concentrations. Contribution of mattress covers to emission fluxes was also examined. Eighteen VOCs were quantified with fluxes ranging from 10–4 to 10–1 mg/(h·m–2). Under sleeping conditions VOC emissions increased significantly. Elevated heat seems to be the major contributor to the enhanced emissions, compared to elevated relative humidity and CO2 concentration. Exposure levels estimated for sleeping child/infant indicate that SME can be a significant contributor to VOC exposure, yielding concerning exposure levels for few compounds. Furthermore, the present study demonstrates the strong dependency of sleeping person exposure on air exchange rate between his breathing zone and bedroom air (λBZ).