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Building related health effects or symptoms (BRS), known also as sick-building syndrome (SBS), are a phenomenon that is not well understood. In this study, air samples from 51 rooms associated with BRS and 34 control rooms were collected on multi-sorbent tubes and analyzed by a non-target approach using comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry techniques. The large amount of data gathered was analyzed using multivariate statistics (principle component analysis (PCA) and partial least squares (PLS)). This new analysis approach revealed that in rooms where people experienced BRS, petrochemicals and chemicals emitted from plastics were abundant, whereas in rooms where people did not experience BRS, flavor and fragrance compounds were abundant. Among the petrochemicals benzene and 2-butoxyethanol were found in higher levels in rooms where people experienced BRS. The levels of limonene were sometimes in the range of reported odor thresholds, and similarly 3-carene and beta-myrcene were found in higher concentrations in indoor air of rooms where people did not experience BRS. It cannot be ruled out that these compounds may have influenced the perceived air quality. However, the overall variability in air concentrations was large and it was not possible to accurately predict if the air in a particular room could cause BRS or not. Unlabelled Image • Non-target screening of indoor air and multivariate statistics were combined. • Volatile organic compounds (VOCs) and building related symptoms (BRS) were studied. • Petrochemicals were predominant in rooms where people experienced BRS. • Flavor and fragrances were abundant in rooms where people did not experience BRS. • Large temporal (one year) fluctuations in VOC composition indoors were noted. [ABSTRACT FROM AUTHOR]