Nonwoven membranes of poly(ε‐caprolactone) (PCL) and chitosan (CS) were produced according to the two methods: by blending the polymers in solution followed by electrospinning – polymer blending method – and by simultaneous deposition of fibers electrospun from separate solutions – fiber blending (FB) method. The two production methods were compared by assessing fiber morphology, mass loss, swelling degree, water contact angle, and mechanical properties of the resulting electrospun membranes. Furthermore, the adhesion, proliferation, and morphology of human dermal fibroblasts on the eight types of scaffold produced were evaluated to assess if the blending method used would influence cell–scaffold interaction. Cell adhesion to the different scaffolds lied in the interval 40–60%, with the CS scaffold presenting the lowest value. Interestingly, cell proliferation was the same when comparing polymer blending and FB scaffolds having 3:1 or 1:3 PCL/CS ratios but very different when the ratio was 1:1 – the FB scaffold sustained a proliferation rate double that of the polymer blending scaffold. This work shows that, when blending polymers to improve the properties of a scaffold for tissue engineering or 3D cell culture, their spatial distribution may considerably affect scaffold's properties and should be considered as another parameter requiring optimization. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47191.