In this work, chitosan and collagen-chitosan porous scaffolds were produced by the freeze drying method and characterized as potential skin substitutes. Their beneficial effects on soft tissues justify the choice of both collagen and chitosan. Samples were characterized using scanning electron microscope, Fourier Transform InfraRed Spectroscopy (FTIR) and thermogravimetry (TG). The in vitro cytocompatibility of chitosan and collagen-chitosan scaffolds was evaluated with three different assays. Phenol and titanium powder were used as positive and negative controls, respectively. Scanning electron microscopy revealed the highly interconnected porous structure of the scaffolds. The addition of collagen to chitosan increased both pore diameter and porosity of the scaffolds. Results of FTIR and TG analysis indicate that the two polymers interact yielding a miscible blend with intermediate thermal degradation properties. The reduction of XTT ((2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) and the uptake of Neutral Red (NR) were not affected by the blend or by the chitosan scaffold extracts, but the blend and the titanium powder presented greater incorporation of Crystal Violet (CV) than phenol and chitosan alone. In conclusion, collagen-chitosan scaffolds produced by freeze-drying methods were cytocompatible and presented mixed properties of each component with intermediate thermal degradation properties.