Plasma treatment of substrate surfaces can be utilized to improve adhesion of cells to tissue-engineered scaffolds. The purpose of this study was to enhance cell adhesion to non-woven poly(L-lactic acid) (PLLA) scaffolds using oxygen plasma treatment to increase surface hydroxyl groups and thereby enhance substrate hydrophilicity. It was hypothesized that oxygen plasma treatment would increase the number of adipose-derived human mesenchymal stem cells (hMSCs) that adhered to melt-blown, non-woven PLLA scaffolds without affecting cell viability. The number of cells that adhered to the oxygen plasma-treated (10 min at 100 W) or untreated PLLA scaffolds was assessed at 2, 4, 8, 12, 24 and 48 h post-seeding via DNA analysis. Cell viability and morphology were also assessed at 2, 4, 8, 12 and 24 h post-seeding via a live/dead assay and hematoxylin staining, respectively. Oxygen plasma treatment decreased the contact angle of water from 75.6 degrees to 58.2 degrees , indicating an increase in the surface hydrophilicity of PLLA. The results of the DNA analysis indicated that there was an increased number of hMSCs on oxygen plasma treated scaffolds for two of the three donors. In addition, oxygen plasma treatment promoted a more even distribution of hMSCs throughout the scaffold and enhanced cell spreading at earlier time points without altering cell viability. This early induction of cell spreading and the uniform distribution of cells, in turn, may increase future proliferation and differentiation of hMSCs under conditions that simulate the microenvironment in vivo.