Rapid healing of acute and chronic skin defects is an important objective. In the present work, we report on the design and feasibility of a co-culture system for fibroblasts and keratinocytes by using electrospun polycaprolactone (PCL) scaffolds. Specifically, we quantified the effect of scaffold fiber diameter on keratinocyte attachment, proliferation and differentiation along with collagen secretion by fibroblasts post vacuum seeding with fibroblasts at various depths. The results show that fibroblasts secrete more collagen and keratinocytes differentiate more on 400 nm scaffolds than on 1000 nm scaffolds. Also, fibroblasts co-cultured with keratinocytes provide increased collagen secretion and keratinocyte differentiation. These results suggest that the fiber architecture can be a useful parameter in skin tissue engineering.