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A critical aspect in the development of biomaterials is the optimization of their surface properties to achieve an adequate cell response. In the present work, electrospun polycaprolactone nanofiber meshes (NFMs) are treated by radio‐frequency (RF) plasma using different gases (Ar or O₂), power (20 or 30 W), and exposure time (5 or 10 min). Morphological and roughness analysis show topographical changes on the plasma‐treated NFMs. X‐ray photoelectron spectroscopy (XPS) results indicate an increment of the oxygen‐containing groups, mainly OH and CO, at the plasma‐treated surfaces. Accordingly, the glycerol contact angle results demonstrate a decrease in the hydrophobicity of plasma‐treated meshes, particularly in the O₂‐treated ones. Three model cell lines (fibroblasts, chondrocytes, and osteoblasts) are used to study the effect of plasma treatments over the morphology, cell adhesion, and …