Nerve guides are cylindrical conduits of either biologically based or synthetic materials that are used to bridge nerve defects. While it is well known that a critical aspect of nerve regeneration is the delivery of oxygen and nutrients to the surviving nerve tissue, several guide parameters that determine the permeability of nerve guides to nutrients are often overlooked. We have reproducibly manufactured poly(caprolactone) (PCL) nerve guides of tailored porosity percentage, wall thickness and pore diameter through a dip-coating/salt-leaching technique. In this study, these three parameters were varied to measure the response of glucose and lysozyme diffusion through the guide wall. In addition, nerve guide permeability following protein fouling studies was examined. Based on the results from this study, it was determined that at high porosity percentages (80%), decreasing the pore diameter (10-38microm) was a measurable method of decreasing the lysozyme permeability of PCL nerve guides while not creating a loss of glucose permeability. PCL fouling studies were used to fine-tune the desirable nerve guide wall thickness. Results indicated that nerve guides 0.6mm thick decreased the loss of lysozyme to almost 10% without significantly diminishing glucose (nutrient) permeability. These results will be utilized to optimize nerve guide parameters for future in vivo applications.