To determine whether the surface free energy of polymer materials influences the spreading and growth of cells, surface free energies of 13 polymers and glass were related to spreading and growth of human skin fibroblasts. Experiments were performed in both the presence and absence of serum proteins. We calculated the surface free energy from contact angles of phosphate-buffered saline (PBS), n-propanol/PBS mixtures, and α-bromonaphthalene on the polymers, using the concept of polar and dispersion components accounting for spreading pressures. Cell spreading and substratum surface free energy (γs) showed a characteristic sigmoid relationship both in the presence and in the absence of serum proteins; good spreading only occurred when γs was higher than approximately 57 erg · cm−2. In the presence of serum proteins, cell spreading is similar on most materials; only few materials show relatively high cell spreading. Cell growth in the presence of serum proteins did not differ significantly on the various polymers with reference to their γs values. In contrast, two groups of polymers could be distinguished in the absence of serum with respect to cell growth. The first group showed increasing γs, whereas the second group showed consistently low cell growth. The results demonstrate the complex relationship between cell spreading and substratum surface free energy as well as the role of serum proteins in modifying the surface characteristics of polymers in relation to cell spreading and growth.