In the frame of the OFFICAIR project, indoor and outdoor PM2.5 samples were collected in office buildings across Europe in two sampling campaigns (summer and winter). The ability of the particles to deplete physiologically relevant antioxidants (ascorbic acid (AA), reduced glutathione (GSH)) in a synthetic respiratory tract lining fluid, i.e., oxidative potential (OP), was assessed. Furthermore, the link between particulate OP and the concentration of the PM constituents was investigated.The mean indoor PM2.5 mass concentration values were substantially lower than the related outdoor values with a mean indoor/outdoor PM2.5 mass concentration ratio of 0.62 and 0.61 for the summer and winter campaigns respectively. The OP of PM2.5 varied markedly across Europe with the highest outdoor OPAA m−3 and OPGSH m−3 (% antioxidant depletion/m3 air) values obtained for Hungary, while PM2.5 collected in Finland exhibited the lowest values. Seasonal variation could be observed for both indoor and outdoor OPAA m−3 and OPGSH m−3 with higher mean values during winter. The indoor/outdoor OPAA m−3 and OPGSH m−3 ratios were less than one with 4 and 17 exceptions out of the 40 cases respectively. These results indicate that indoor air is generally less oxidatively challenging than outdoors. Correlation analysis revealed that trace elements play an important role in determining OP, in particular, the Cu content. Indoor air chemistry might affect OP since weaker correlations were obtained for indoor PM2.5. Our findings also suggest that office workers may be exposed to health relevant PM constituents to a different extent within the same building.