The aim of this study has been to fabricate a hybrid electrospun nanofibrous scaffold composed of poly(lactic-co-glycolic) acid (PLGA)/fibrin polymers to be used as a skin substitute and analyze its physical and biological properties. Fibrin was obtained from rat blood plasma, characterized and solubilized in formic acid. The final electrospinning solution concentration was 40% PLGA (w/v) and 1% fibrin (w/v). To improve spinnability, 3% PEG (w/v) was added. The scaffolds were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Water contact angle, maximum elongation, thermal stability, degree of swelling, blood compatibility, cytotoxicity and cell viability were analyzed. The characterization by SEM showed randomly oriented nanofibers with a mean diameter of 639.8 +/- 241.8 nm for the PLGA/fibrin and 1051.0 +/- 290.2 nm for the PLGA. FTIR spectra confirmed the presence of fibrin in the mats. Fibrin incorporation reduced the water contact angle from 118.9 +/- 2.9 to 111.1 +/- 2.8. The fibrin increased tensile strength and decreased elongation at break. The scaffolds demonstrated blood compatibility and fibrin incorporation improved cell adhesion and viability when direct and indirect MTT analyses were carried out. Thus, it can be concluded that the PLGA/fibrin mat is a promising material for use as a skin substitute.